P L McGeer

Summary

Affiliation: University of British Columbia
Country: Canada

Publications

  1. ncbi request reprint Innate immunity, local inflammation, and degenerative disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research at the University of British Columbia, Vancouver, BC, V6T 1Z3, Canada
    Sci Aging Knowledge Environ 2002:re3. 2002
  2. pmc Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis
    Judith Miklossy
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    J Neuroinflammation 5:40. 2008
  3. pmc Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease
    Anastazija Gnjec
    Centre of Excellence for Alzheimer s Disease Research and Care, Faculty of Computing, Health and Science, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, 6027, WA, Australia
    J Neuroinflammation 5:36. 2008
  4. ncbi request reprint Local neuroinflammation and the progression of Alzheimer's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurovirol 8:529-38. 2002
  5. ncbi request reprint Expression of COX-1 and COX-2 mRNAs in atherosclerotic plaques
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Exp Gerontol 37:925-9. 2002
  6. doi request reprint The alpha-synuclein burden hypothesis of Parkinson disease and its relationship to Alzheimer disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B C, Canada V6T 1Z3
    Exp Neurol 212:235-8. 2008
  7. ncbi request reprint Inflammation, autotoxicity and Alzheimer disease
    P L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, B C, Canada
    Neurobiol Aging 22:799-809. 2001
  8. ncbi request reprint Polymorphisms in inflammatory genes and the risk of Alzheimer disease
    P L McGeer
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Arch Neurol 58:1790-2. 2001
  9. ncbi request reprint Cyclo-oxygenase-2 inhibitors: rationale and therapeutic potential for Alzheimer's disease
    P L McGeer
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Drugs Aging 17:1-11. 2000
  10. ncbi request reprint Autotoxicity and Alzheimer disease
    P L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3
    Arch Neurol 57:789-90. 2000

Detail Information

Publications123 found, 100 shown here

  1. ncbi request reprint Innate immunity, local inflammation, and degenerative disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research at the University of British Columbia, Vancouver, BC, V6T 1Z3, Canada
    Sci Aging Knowledge Environ 2002:re3. 2002
    ..NSAIDs inhibit the production of prostaglandin inflammatory mediators, but powerful new therapeutic agents might be developed by targeting more critical inflammatory mechanisms, especially the complement system...
  2. pmc Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis
    Judith Miklossy
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    J Neuroinflammation 5:40. 2008
    ..We investigated whether a similar situation may occur in Lyme neuroborreliosis...
  3. pmc Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease
    Anastazija Gnjec
    Centre of Excellence for Alzheimer s Disease Research and Care, Faculty of Computing, Health and Science, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, 6027, WA, Australia
    J Neuroinflammation 5:36. 2008
    ..In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases...
  4. ncbi request reprint Local neuroinflammation and the progression of Alzheimer's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
    J Neurovirol 8:529-38. 2002
    ....
  5. ncbi request reprint Expression of COX-1 and COX-2 mRNAs in atherosclerotic plaques
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Exp Gerontol 37:925-9. 2002
    ..Accordingly, COX-2 inhibitors may reduce the degree of inflammation and protect against future cardiovascular events...
  6. doi request reprint The alpha-synuclein burden hypothesis of Parkinson disease and its relationship to Alzheimer disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B C, Canada V6T 1Z3
    Exp Neurol 212:235-8. 2008
  7. ncbi request reprint Inflammation, autotoxicity and Alzheimer disease
    P L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, B C, Canada
    Neurobiol Aging 22:799-809. 2001
    ..Inhibitors of mediators closer to the core processes might offer even greater therapeutic promise. Some theoretical opportunities are suggested, based on intervention in the action of the above mentioned mediators...
  8. ncbi request reprint Polymorphisms in inflammatory genes and the risk of Alzheimer disease
    P L McGeer
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Arch Neurol 58:1790-2. 2001
    ..Such information could lead to strategies for therapeutic intervention in the early stages of such disorders...
  9. ncbi request reprint Cyclo-oxygenase-2 inhibitors: rationale and therapeutic potential for Alzheimer's disease
    P L McGeer
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Drugs Aging 17:1-11. 2000
    ..These results emphasise that the appropriate target for NSAID trials in AD is COX-1, but they also indicate that there would be no contraindication to the use of those traditional NSAIDs which have mixed COX-1/COX-2 inhibiting activity...
  10. ncbi request reprint Autotoxicity and Alzheimer disease
    P L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3
    Arch Neurol 57:789-90. 2000
    ..Even in vertebrates, however, the innate immune system is the first line of defense. Much more needs to be learned about the operation of the innate immune system in health and disease. Arch Neurol. 2000...
  11. ncbi request reprint Brain inflammation in Alzheimer disease and the therapeutic implications
    E G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B C, V6T 1Z3, Canada
    Curr Pharm Des 5:821-36. 1999
    ..The complement system, microglia and cytokines are key components. This review summarizes the present state of knowledge on the immune system elements found in AD brain...
  12. ncbi request reprint Glial reactions in Parkinson's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    Mov Disord 23:474-83. 2008
    ..Further research concerning glial reactions in PD may lead to disease-modifying therapeutic approaches...
  13. ncbi request reprint Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, Division of Neurology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Ann Neurol 54:599-604. 2003
    ..The mechanism is unknown but could have important implications regarding the cause of Parkinson's disease and possible approaches to therapy...
  14. ncbi request reprint Association of interleukin-1 beta polymorphisms with idiopathic Parkinson's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research and the Movement Disorders Center, University of British Columbia, Vancouver, B C, Canada
    Neurosci Lett 326:67-9. 2002
    ..65, P=0.0019). A significant increase was not found for the IL-alpha T genotype (chi(2)=1.32, P=0.23), although there was a trend towards more frequent expression of the T allele...
  15. ncbi request reprint Inflammation and the degenerative diseases of aging
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Ann N Y Acad Sci 1035:104-16. 2004
    ..Thus, full therapeutic doses of NSAIDs, or combinations of anti-inflammatory agents, are needed to achieve the suggested neurological benefits...
  16. ncbi request reprint NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    Neurobiol Aging 28:639-47. 2007
    ..Further clinical investigations with relatively high doses of traditional NSAIDs might be warranted, although significant side effects should be anticipated...
  17. ncbi request reprint Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver BC, Canada
    J Alzheimers Dis 9:271-6. 2006
    ..Future directions should include a search for other inflammatory mediators in AD and exploitation of current knowledge to improve available treatments...
  18. ncbi request reprint Immunotherapy for Alzheimer's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research at the University of British Columbia, Vancouver, BC V6T 1Z3, Canada
    Sci Aging Knowledge Environ 2004:pe29. 2004
    ..Because both pro- and anti-inflammatory activation of immune cells are possible, stimulating the phagocytic action of microglia while simultaneously stimulating anti-inflammatory activity might be beneficial in AD...
  19. doi request reprint The ALS/PDC syndrome of Guam: potential biomarkers for an enigmatic disorder
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    Prog Neurobiol 95:663-9. 2011
    ..Identification of biomarkers for premortem diagnosis would be helpful in management as well as in revealing the true etiology...
  20. ncbi request reprint Immunohistochemical analyses of fibroblast growth factor receptor-1 in the human substantia nigra. Comparison between normal and Parkinson's disease cases
    D G Walker
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, British Columbia, Canada
    Brain Res 794:181-7. 1998
    ..FGFR-1 immunoreactivity was also detected in many of the residual SN neurons in most of the idiopathic PD cases. These results indicate that FGFR-1 immunoreactivity, and possibly FGF binding activity, is retained in DA neurons in PD...
  21. ncbi request reprint Induction of complement C9 messenger RNAs in human neuronal cells by inflammatory stimuli: relevance to neurodegenerative disorders
    A Klegeris
    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Exp Gerontol 36:1179-88. 2001
    ....
  22. ncbi request reprint Tetrahydroaminoacridine potentiates neurotoxicity of quinolinic acid in rat striatum
    S G Zhu
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Neurosci Lett 95:252-6. 1988
    ..A larger dose (10 mg/kg) THA had no significant effect. The results are discussed in terms of THA's binding to various elements of the NMDA/sigma receptor complex and reported data on such binding are confirmed...
  23. ncbi request reprint Role of ICAM-1 in persisting inflammation in Parkinson disease and MPTP monkeys
    J Miklossy
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T1Z3
    Exp Neurol 197:275-83. 2006
    ..The presence of ICAM-1-positive reactive astrocytes in Parkinson disease and MPTP-treated monkeys is indicative of a sustained inflammatory process and suggests that antiinflammatory agents may have a place in PD therapy...
  24. ncbi request reprint 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in Alzheimer and control brain
    K Yasojima
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada
    Neuroreport 12:2935-8. 2001
    ..We conclude that brain has a robust capacity to synthesize cholesterol which appears to be unaffected by AD pathology...
  25. ncbi request reprint Inflammatory cytokine levels are influenced by interactions between THP-1 monocytic, U-373 MG astrocytic, and SH-SY5Y neuronal cell lines of human origin
    A Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
    Neurosci Lett 313:41-4. 2001
    ....
  26. ncbi request reprint Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Neurobiol Aging 23:787-94. 2002
    ....
  27. ncbi request reprint High stability of mRNAs postmortem and protocols for their assessment by RT-PCR
    K Yasojima
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Brain Res Brain Res Protoc 8:212-8. 2001
    ..Reliable mRNA values may be obtained from postmortem brain with long autolysis times provided the tissue has been kept in the cold, and from frozen tissues for 1-2 h after thawing...
  28. ncbi request reprint Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells
    A Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    J Neuroimmunol 78:152-61. 1997
    ..These data indicate that inflammatory stimuli may increase extracellular glutamate while antiinflammatory drugs decrease it...
  29. pmc Generation of C-reactive protein and complement components in atherosclerotic plaques
    K Yasojima
    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3 Canada
    Am J Pathol 158:1039-51. 2001
    ..Because CRP is a complement activator, and activated complement attacks cells in plaque tissue, these data provide evidence of a self-sustaining autotoxic mechanism operating within the plaques as a precursor to thrombotic events...
  30. ncbi request reprint Effect of MK-801, kynurenate, glycine, dextrorphan and 4-acetylpyridine on striatal toxicity of quinolinate
    S G Zhu
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Brain Res 481:356-60. 1989
    ..Glycine appeared to potentiate the effect of high doses of quinolinic acid on ChAT and the other pretreatments tested (dextrorphan, dextromethorphan, 4-acetylpyridine) had no significant effect...
  31. ncbi request reprint Expression of the proto-oncogene Ret, a component of the GDNF receptor complex, persists in human substantia nigra neurons in Parkinson's disease
    D G Walker
    Kinsmen Laboratory of Neurological Research and Neurodegenerative Disease Centre, University of British Columbia, Vancouver, BC, Canada
    Brain Res 792:207-17. 1998
    ..Ret expression by microglia was confirmed by immunoblot analysis on the human THP-1 macrophage type cell line. However, these cells did not express the mRNA for GDNFRalpha, the other component of the GDNF receptor complex...
  32. ncbi request reprint Transgenic mice overexpressing amyloid beta protein are an incomplete model of Alzheimer disease
    Claudia Schwab
    Kinsmen Laboratory of Neurological Research, Division of Neurology, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Exp Neurol 188:52-64. 2004
    ..Therapeutic strategies for the treatment of AD based on tg mouse models that overexpress Abeta may be limited in their application...
  33. ncbi request reprint Interleukin 1alpha and interleukin 6 protect human neuronal SH-SY5Y cells from oxidative damage
    Christopher J Bissonnette
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    Neurosci Lett 361:40-3. 2004
    ..These data indicate that IL-1alpha and IL-6 can, under appropriate circumstances, protect neurons from oxidative damage in addition to their well-known action of stimulating inflammation...
  34. doi request reprint Enduring involvement of tau, beta-amyloid, alpha-synuclein, ubiquitin and TDP-43 pathology in the amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC)
    Judith Miklossy
    Kinsmen Laboratory of Neurological Research, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada
    Acta Neuropathol 116:625-37. 2008
    ..The results obtained may help to define the commonality of the Guam disease with other tangle forming disorders and may help in monitoring the epidemiological changes that are taking place...
  35. ncbi request reprint Enhancement of immunoreactivity for NF-kappa B in human cerebral infarctions
    K Terai
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Brain Res 739:343-9. 1996
    ..Capillary staining for NF-kappa B was weak and did not differ significantly between affected and unaffected areas. These results suggest that enhanced expression of astrocytic NF-kappa B occurs in cerebral infarcted areas...
  36. ncbi request reprint Toxicity of human THP-1 monocytic cells towards neuron-like cells is reduced by non-steroidal anti-inflammatory drugs (NSAIDs)
    A Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Neuropharmacology 38:1017-25. 1999
    ..It is suggested that inhibition of monocyte cytotoxicity might be responsible for the apparent beneficial effects of NSAIDs in Alzheimer's disease...
  37. ncbi request reprint Inhibitory action of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK 11195) on some mononuclear phagocyte functions
    A Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    Biochem Pharmacol 59:1305-14. 2000
    ..Since PK 11195 readily enters the brain, it may be beneficial in treating central as well as peripheral inflammatory diseases...
  38. ncbi request reprint The pentraxins: possible role in Alzheimer's disease and other innate inflammatory diseases
    E G McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, V6T 1Z3, Vancouver, B C, Canada
    Neurobiol Aging 22:843-8. 2001
    ..As such, they may be prime targets for therapeutic intervention...
  39. ncbi request reprint Enhancement of immunoreactivity for NF-kappa B in the hippocampal formation and cerebral cortex of Alzheimer's disease
    K Terai
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Brain Res 735:159-68. 1996
    ..There was no difference between AD and control cases in the staining of glial cells and vascular walls. These results suggest that enhanced expression of neuronal NF-kappa B occurs in areas affected by AD pathology...
  40. ncbi request reprint Transplantation of cultured human adrenal chromaffin cells into 6-hydroxydopamine-lesioned rat brain
    H Kamo
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Synapse 1:324-8. 1987
    ..This transplantation of cultured human fetal cells to an animal model may provide the necessary basic experimental system for assessing the possible utility of human neuronal transplants...
  41. ncbi request reprint Apolipoprotein E4 (ApoE4) but not ApoE3 or ApoE2 potentiates beta-amyloid protein activation of complement in vitro
    P L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Brain Res 749:135-8. 1997
    ..This ApoE4-specific enhancement of complement activation by A beta may relate to its role in increasing the risk of late-onset AD...
  42. ncbi request reprint Complement components, but not complement inhibitors, are upregulated in atherosclerotic plaques
    K Yasojima
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver
    Arterioscler Thromb Vasc Biol 21:1214-9. 2001
    ..These data indicate that it is primarily the classical, not the alternative pathway, that is activated in plaques and that key inhibitors are not upregulated to defend against this activation...
  43. pmc Reduction of human monocytic cell neurotoxicity and cytokine secretion by ligands of the cannabinoid-type CB2 receptor
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Br J Pharmacol 139:775-86. 2003
    ..5 Specific CB2 receptor ligands could be useful anti-inflammatory agents, while avoiding the neurotoxic and psychoactive effects of CB1 receptor ligands such as Delta(9)-THC...
  44. doi request reprint Interferon-gamma-dependent cytotoxic activation of human astrocytes and astrocytoma cells
    Sadayuki Hashioka
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1W5 Canada
    Neurobiol Aging 30:1924-35. 2009
    ..These findings suggest that activated astrocytes may become neurotoxic when stimulated by IFN-gamma and may therefore exacerbate the pathology in a spectrum of neurodegenerative diseases...
  45. ncbi request reprint Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders
    Claudia Schwab
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    J Alzheimers Dis 13:359-69. 2008
    ..From a therapeutic point of view it is desirable to find methods of tipping the balance towards an anti-inflammatory state for both types of glia...
  46. ncbi request reprint Clusterin as a marker for ischaemic Purkinje cells in human brain
    O Yasuhara
    Kinsmen Laboratory of Neurological Research, Vancouver, B C, Canada
    Neurodegeneration 3:325-9. 1994
    ..The results provide additional evidence supporting an association of clusterin with dying neurons in human brain...
  47. ncbi request reprint Relationship between beta amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain
    K Yasojima
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, V6T 1Z3, Vancouver, Canada
    Brain Res 919:115-21. 2001
    ..Overall, the data indicate that effectiveness of degradation by neprilysin may be a key factor in determining whether Abeta deposits develop...
  48. ncbi request reprint beta-amyloid protein enhances macrophage production of oxygen free radicals and glutamate
    A Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    J Neurosci Res 49:229-35. 1997
    ..Such mechanisms could contribute to the pathogenesis of neurodegenerative disorders, including Alzheimer's disease...
  49. ncbi request reprint Brain microglia constitutively express beta-2 integrins
    H Akiyama
    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, Faculty of Medicine, University of British Columbia, Vancouver, Canada
    J Neuroimmunol 30:81-93. 1990
    ..They provide further evidence of an inflammatory response of brain tissue in Alzheimer disease. The microglia were found to make up 9-12% of the total glial population in gray matter and 7.5-9% in white matter...
  50. ncbi request reprint Casein kinase 1 delta is associated with pathological accumulation of tau in several neurodegenerative diseases
    C Schwab
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, B C, Canada
    Neurobiol Aging 21:503-10. 2000
    ..The colocalization of the kinase Cki delta and its apparent substrate tau suggests a function for Cki delta in the abnormal processing of tau...
  51. ncbi request reprint Microglial response to 6-hydroxydopamine-induced substantia nigra lesions
    H Akiyama
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Brain Res 489:247-53. 1989
    ..Combined observation of these markers in diseased brain tissue can provide clues as to the stage of the pathology being observed...
  52. ncbi request reprint Marked increase in cyclooxygenase-2 in ALS spinal cord: implications for therapy
    K Yasojima
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada
    Neurology 57:952-6. 2001
    ..Taken in conjunction with evidence of a neuroprotective effect of COX-2 inhibitors in certain animal models and in organotypic cultures, the data are supportive of a possible future role for COX-2 inhibitors in the treatment of ALS...
  53. ncbi request reprint S- but not R-enantiomers of flurbiprofen and ibuprofen reduce human microglial and THP-1 cell neurotoxicity
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    J Neuroimmunol 152:73-7. 2004
    ..We found S- but not R-enantiomers to be protective at low concentrations, which is consistent with a COX-dependent mechanism...
  54. ncbi request reprint Modulation of human microglia and THP-1 cell toxicity by cytokines endogenous to the nervous system
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
    Neurobiol Aging 26:673-82. 2005
    ..These data suggest that antagonists of cytokine receptors, as well as inhibitors of their intracellular pathways may be effective anti-inflammatory agents...
  55. ncbi request reprint Non-steroidal anti-inflammatory drugs (NSAIDs) and other anti-inflammatory agents in the treatment of neurodegenerative disease
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Curr Alzheimer Res 2:355-65. 2005
    ..Therefore combination therapy with other anti-inflammatory agents that work through different mechanisms of action might prove to be a superior therapeutic strategy...
  56. doi request reprint Prolyl endopeptidase is revealed following SILAC analysis to be a novel mediator of human microglial and THP-1 cell neurotoxicity
    Andis Klegeris
    Unit of Biology and Physical Geography, Barber School of Arts and Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada
    Glia 56:675-85. 2008
    ..We found both to be partially protective in a concentration-dependent manner. Inhibition of PEP may be a therapeutic approach to neurodegenerative disorders including Alzheimer and Parkinson diseases...
  57. doi request reprint Hydrogen sulfide-releasing NSAIDs attenuate neuroinflammation induced by microglial and astrocytic activation
    MoonHee Lee
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    Glia 58:103-13. 2010
    ....
  58. doi request reprint Proton pump inhibitors exert anti-inflammatory effects and decrease human microglial and monocytic THP-1 cell neurotoxicity
    Sadayuki Hashioka
    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, The University of British Columbia, Vancouver, BC, Canada
    Exp Neurol 217:177-83. 2009
    ..They suggest that PPIs combined with NSAIDs may be effective in the treatment of a broad spectrum of neurodegenerative diseases associated with activated microglia...
  59. ncbi request reprint Adhesion of exogenous human microglia and THP-1 cells to amyloid plaques of postmortem Alzheimer's disease brain
    Sadayuki Hashioka
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada
    J Alzheimers Dis 14:345-52. 2008
    ..These results suggest that human microglial cells are capable of adhering to and phagocytosing post mortem AD plaque material but activation may be necessary. Astrocytes may further enhance the process...
  60. ncbi request reprint Inflammatory processes in amyotrophic lateral sclerosis
    P L McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Westbrook Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Muscle Nerve 26:459-70. 2002
    ..Anti-inflammatory agents may have a role to play in treating ALS. COX-2 is a particularly attractive target because of its marked increase in ALS spinal cord...
  61. ncbi request reprint Converging perturbed microvasculature and microglial clusters characterize Alzheimer disease brain
    N Jantaratnotai
    Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada
    Curr Alzheimer Res 7:625-36. 2010
    ..Microglial-vascular reciprocal interactions could serve a critical role in the amplification and perpetuation of inflammatory reactivity in AD brain...
  62. ncbi request reprint On the survival time of a tangled neuron in the hippocampal CA4 region in parkinsonism dementia complex of Guam
    C Schwab
    Kinsmen Laboratory of Neurological Research, Movement Disorders Centre, University of B C, Vancouver, Canada
    Neurobiol Aging 20:57-63. 1999
    ..The results varied from 0.13 years for the most rapidly progressing case to 7.98 years for the most slowly developing case. The average for 8 cases was 2.51 years...
  63. ncbi request reprint The importance of inflammatory mechanisms in Alzheimer disease
    E G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Exp Gerontol 33:371-8. 1998
    ..Therapeutic intervention in key inflammatory processes holds great promise for the amelioration of AD and possibly other neurodegenerative disorders...
  64. ncbi request reprint Interaction of various intracellular signaling mechanisms involved in mononuclear phagocyte toxicity toward neuronal cells
    A Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    J Leukoc Biol 67:127-33. 2000
    ..It is concluded that the stimulants activated multiple intracellular pathways, and that combination therapies inhibiting these pathways might be beneficial for treating neurodegenerative disorders...
  65. ncbi request reprint Innate immunity in Alzheimer's disease: a model for local inflammatory reactions
    E G McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry University of British Columbia, Vancouver, BC V6T 1Z3
    Mol Interv 1:22-9. 2001
    ..In the case of Alzheimer's disease, inflammatory processes thus have the potential for turning a relatively slowly progressing condition into one characterized by rapid neurodegeneration...
  66. ncbi request reprint Enhancement of progenitor cell division in the dentate gyrus triggered by initial limbic seizures in rat models of epilepsy
    E Nakagawa
    Molecular Neuroscience Research Center, and Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan
    Epilepsia 41:10-8. 2000
    ..We investigated which stage of epileptogenesis is critical for eliciting progenitor cell division and whether seizure-induced neuronal degeneration is responsible for the enhancement of progenitor cell division...
  67. doi request reprint Differential expression of interferon-gamma receptor on human glial cells in vivo and in vitro
    Sadayuki Hashioka
    Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada
    J Neuroimmunol 225:91-9. 2010
    ....
  68. ncbi request reprint Abeta immunotherapy and other means to remove amyloid
    Edith G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, B C, Canada
    Curr Drug Targets CNS Neurol Disord 4:569-73. 2005
    ..Whether they would affect the more consolidated, cross-linked Abeta of AD and, if they did, whether that would really prove an effective treatment for the disease remains for future research to determine...
  69. ncbi request reprint The role of anti-inflammatory agents in Parkinson's disease
    Edith G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    CNS Drugs 21:789-97. 2007
    ..Whether such drugs will slow the process of Parkinson's disease or reduce the high risk of dementia in such patients remains to be determined in future work...
  70. pmc Effects of hydrogen sulfide-releasing L-DOPA derivatives on glial activation: potential for treating Parkinson disease
    MoonHee Lee
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 285:17318-28. 2010
    ..The H(2)S-releasing L-DOPA hybrid molecules also inhibited MAO B activity. They may be useful for the treatment of PD because of their significant antiinflammatory, antioxidant, and neuroprotective properties...
  71. ncbi request reprint Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide
    Sadayuki Hashioka
    Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi 3 1 1, Higashi ku, Fukuoka, 812 8582 Japan
    Exp Neurol 206:33-42. 2007
    ..On the other hand, the mood stabilizer and anti-manic agent lithium chloride has mixed effects on IFN-gamma-induced microglial activation...
  72. ncbi request reprint Increase in core body temperature of Alzheimer's disease patients as a possible indicator of chronic neuroinflammation: a meta-analysis
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    Gerontology 53:7-11. 2007
    ..Such increases have been observed in AD brains. We hypothesized that these increased levels of inflammatory mediators could lead to an increase in core body temperature in AD patients...
  73. ncbi request reprint Alpha-synuclein activates stress signaling protein kinases in THP-1 cells and microglia
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
    Neurobiol Aging 29:739-52. 2008
    ....
  74. doi request reprint Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide
    MoonHee Lee
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada
    Neurobiol Aging 30:1523-34. 2009
    ..H(2)S releasing drugs may have therapeutic potential in neurodegenerative disorders of aging such as Alzheimer disease and Parkinson disease...
  75. ncbi request reprint Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada
    FASEB J 20:2000-8. 2006
    ..5 microM respectively. We hypothesize that the neuroinflammation stimulated by release of an excess of normal alpha-synuclein or by release of its mutated forms can be involved in the pathobiology of PD...
  76. ncbi request reprint Anti-inflammatory effects of antidepressants: possibilities for preventives against Alzheimer's disease
    Sadayuki Hashioka
    Department of Psychiatry, The University of British Columbia, Vancouver, Canada
    Cent Nerv Syst Agents Med Chem 9:12-9. 2009
    ....
  77. doi request reprint Depletion of GSH in glial cells induces neurotoxicity: relevance to aging and degenerative neurological diseases
    MoonHee Lee
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    FASEB J 24:2533-45. 2010
    ....
  78. ncbi request reprint Therapeutic approaches to inflammation in neurodegenerative disease
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    Curr Opin Neurol 20:351-7. 2007
    ..Here we review recent advances in our understanding of one such disorder, Parkinson's disease, in which anti-inflammatory drugs are now becoming a new therapeutic focus...
  79. ncbi request reprint Sparing of age-related macular degeneration in rheumatoid arthritis
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Neurobiol Aging 26:1199-203. 2005
    ..72%). Patients with RA appear to be relatively spared from AMD. We hypothesize that this results from long term antiinflammatory treatment. Genetic or environmental factors could also be responsible...
  80. ncbi request reprint Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    J Leukoc Biol 73:369-78. 2003
    ..The data suggest that inhibition of proinflammatory LT production by 5-LOX inhibition could selectively reduce toxicity of microglial cells and thus be beneficial in neuroinflammatory diseases...
  81. ncbi request reprint Is there a future for vaccination as a treatment for Alzheimer's disease?
    Patrick L McGeer
    Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, BC, V6T 1Z3, Vancouver, Canada
    Neurobiol Aging 24:391-5. 2003
    ..The future of vaccination as a therapy for AD will require surmounting the problems of autoimmune reactions generally and autotoxic complement activation specifically...
  82. ncbi request reprint Clinically tested drugs for Alzheimer's disease
    Edith G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    Expert Opin Investig Drugs 12:1143-51. 2003
    ..There are some promising leads, but more definitive clinical trials are required. Any agent designed to slow progression should clearly be used at an early stage of the disorder; therefore methods of early diagnosis are also essential...
  83. ncbi request reprint Familial British dementia: colocalization of furin and ABri amyloid
    Claudia Schwab
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada
    Acta Neuropathol 106:278-84. 2003
    ..These data suggest that furin may be involved in producing the pathological fragment of ABriPP in vivo and that inhibition of furin might be a method of treating this disorder...
  84. ncbi request reprint Inflammatory processes in Alzheimer's disease
    Edith G McGeer
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Prog Neuropsychopharmacol Biol Psychiatry 27:741-9. 2003
    ..These brain phenomena combined with epidemiological evidence of a protective effect of antiinflammatory agents suggest that such agents may have a role to play in treating the disease...
  85. ncbi request reprint Anti-inflammatory effects of cerebrocrast in a model of rat paw edema and on mononuclear THP-1 cells
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, British Columbia, Canada V6T 1Z3
    Eur J Pharmacol 441:203-8. 2002
    ....
  86. ncbi request reprint Inflammation and neurodegeneration in Parkinson's disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research and the Pacific Parkinson s Research Centre, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Parkinsonism Relat Disord 10:S3-7. 2004
    ..The upregulation appears greater than that found in inflamed arthritic joints. These data support the hypothesis that chronic inflammation may play an important role, if secondary, in the pathogenesis of PD...
  87. ncbi request reprint Chymotrypsin-like proteases contribute to human monocytic THP-1 cell as well as human microglial neurotoxicity
    Andis Klegeris
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    Glia 51:56-64. 2005
    ..The data suggest that certain protease inhibitors could inhibit microglial-mediated toxicity. They might represent a novel class of drugs with benefit in diseases where overactivity of microglia contributes to the pathogenesis...
  88. ncbi request reprint Pharmacologic approaches to the treatment of amyotrophic lateral sclerosis
    Edith G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    BioDrugs 19:31-7. 2005
    ..No breakthrough has yet occurred and present thinking is that combinations of drugs may be required to slow the multifactorial neurodegeneration process effectively...
  89. doi request reprint Neurotoxins released from interferon-gamma-stimulated human astrocytes
    M Lee
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3
    Neuroscience 229:164-75. 2013
    ....
  90. pmc Unmasking of an unusual myelin basic protein epitope during the process of myelin degeneration in humans: a potential mechanism for the generation of autoantigens
    A Matsuo
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Am J Pathol 150:1253-66. 1997
    ..If insults occur that repeatedly expose a region of MBP normally sheltered from immunosurveillance, a self-sustaining immune reaction might result...
  91. ncbi request reprint Expression of complement C4 and C9 genes by human astrocytes
    D G Walker
    Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada
    Brain Res 809:31-8. 1998
    ..In addition it was shown that stimulated astrocytes could also express complement C9 mRNA, though C9 protein was not detectable in culture supernatants...
  92. ncbi request reprint Immunostaining of human brain capillaries by antibodies to very late antigens
    P L McGeer
    Department of Psychiatry, University of British Columbia, Vancouver, Canada
    J Neuroimmunol 26:213-8. 1990
    ..Only residual plasma in vessels was stained with the antibody to fibronectin. Negative staining was obtained with antibodies to the fibronectin receptor VLA-5 and VLA-3. Trace staining was obtained with the antibody to VLA-2...
  93. ncbi request reprint Inflammation of the brain in Alzheimer's disease: implications for therapy
    P L McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    J Leukoc Biol 65:409-15. 1999
    ..Mention will also be made of some recent work on animal models of possible relevance to AD and inflammation...
  94. ncbi request reprint The possible role of complement activation in Alzheimer disease
    Patrick L McGeer
    Kinsmen Laboratory of Neurological Research, Dept of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, BC, V6T 1Z3, Vancouver, Canada
    Trends Mol Med 8:519-23. 2002
    ..Overactive microglia secrete many toxic materials. Inhibition of microglial activation is another potential therapeutic target...
  95. doi request reprint Inflammation in transgenic mouse models of neurodegenerative disorders
    Claudia Schwab
    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T1Z3, Canada
    Biochim Biophys Acta 1802:889-902. 2010
    ..In particular, the mouse models of Alzheimer disease have also led to the development of new therapeutic strategies such as vaccination and modulation of microglial activity...
  96. ncbi request reprint Lrrk2 and chronic inflammation are linked to pallido-ponto-nigral degeneration caused by the N279K tau mutation
    Judith Miklossy
    Kinsmen Laboratory of Neurological Research, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T 1Z3
    Acta Neuropathol 114:243-54. 2007
    ..The results indicate that Lrrk2 is linked to frontotemporal atrophy of PPND type caused by N279K tau mutation. They also show that chronic inflammation is involved in the pathogenesis of N279K/FTDP-17/PPND...
  97. ncbi request reprint Thrombin and prothrombin are expressed by neurons and glial cells and accumulate in neurofibrillary tangles in Alzheimer disease brain
    Tetsuaki Arai
    Department of Psychiatry, Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    J Neuropathol Exp Neurol 65:19-25. 2006
    ..The accumulation of thrombin and prothrombin in NFTs supports the hypothesis that thrombin may be involved in tau proteolysis and that failure to metabolize tau may lead to its aggregation in neurodegenerative diseases...
  98. ncbi request reprint LRRK2 expression in normal and pathologic human brain and in human cell lines
    Judith Miklossy
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada
    J Neuropathol Exp Neurol 65:953-63. 2006
    ..In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders...
  99. ncbi request reprint Inflammation, the complement system and the diseases of aging
    Edith G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada
    Neurobiol Aging 26:94-7. 2005
    ..Stimulation is provided by a variety of inflammatory cytokines. Agents which reduce the intensity of inflammation should have broad spectrum application in degenerative diseases of aging...
  100. ncbi request reprint The future use of complement inhibitors for the treatment of neurological diseases
    E G McGeer
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada
    Drugs 55:739-46. 1998
    ....
  101. pmc Up-regulated production and activation of the complement system in Alzheimer's disease brain
    K Yasojima
    Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada
    Am J Pathol 154:927-36. 1999
    ....