Benoit I Giasson

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Mutations in LRRK2 as a cause of Parkinson's disease
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    Neurosignals 16:99-105. 2008
  2. ncbi request reprint Mitochondrial injury: a hot spot for parkinsonism and Parkinson's disease?
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Sci Aging Knowledge Environ 2004:pe42. 2004
  3. ncbi request reprint Biochemical and pathological characterization of Lrrk2
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Ann Neurol 59:315-22. 2006
  4. ncbi request reprint Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome-mediated conformational alterations
    Erin H Norris
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:21212-9. 2005
  5. ncbi request reprint Cytosolic catechols inhibit alpha-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates
    Joseph R Mazzulli
    The Joseph Stokes Jr Research Institute, The Children s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 26:10068-78. 2006
  6. ncbi request reprint Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein
    Amanda J Mishizen-Eberz
    Department of Neurology, University of Pennsylvania and The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 44:7818-29. 2005
  7. pmc Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutations
    Jason P Covy
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    Mov Disord 24:32-9. 2009
  8. ncbi request reprint Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration
    Ikuru Yazawa
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Neuron 45:847-59. 2005
  9. pmc Convergence of heat shock protein 90 with ubiquitin in filamentous alpha-synuclein inclusions of alpha-synucleinopathies
    Kunihiro Uryu
    The Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104 4283, USA
    Am J Pathol 168:947-61. 2006
  10. pmc Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    J Neuropathol Exp Neurol 67:402-16. 2008

Collaborators

Detail Information

Publications59

  1. ncbi request reprint Mutations in LRRK2 as a cause of Parkinson's disease
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    Neurosignals 16:99-105. 2008
    ....
  2. ncbi request reprint Mitochondrial injury: a hot spot for parkinsonism and Parkinson's disease?
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Sci Aging Knowledge Environ 2004:pe42. 2004
    ....
  3. ncbi request reprint Biochemical and pathological characterization of Lrrk2
    Benoit I Giasson
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Ann Neurol 59:315-22. 2006
    ..The studies herein explore the biological and pathological properties of Lrrk2...
  4. ncbi request reprint Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome-mediated conformational alterations
    Erin H Norris
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Institute on Aging, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:21212-9. 2005
    ..Thus, decreased dopamine levels in substantia nigra neurons might promote alpha-syn aggregation in Parkinson's disease...
  5. ncbi request reprint Cytosolic catechols inhibit alpha-synuclein aggregation and facilitate the formation of intracellular soluble oligomeric intermediates
    Joseph R Mazzulli
    The Joseph Stokes Jr Research Institute, The Children s Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 26:10068-78. 2006
    ..These data indicate that intraneuronal dopamine levels can be a major modulator of alpha-syn aggregation and inclusion formation, with important implications on the selective degeneration of these neurons in Parkinson's disease...
  6. ncbi request reprint Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein
    Amanda J Mishizen-Eberz
    Department of Neurology, University of Pennsylvania and The Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 44:7818-29. 2005
    ..These results provide insight into possible disease mechanisms underlying synucleinopathies since the formation of alpha-syn fibrils could be causally linked to the onset/progression of these disorders...
  7. pmc Clinical and pathological characteristics of patients with leucine-rich repeat kinase-2 mutations
    Jason P Covy
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    Mov Disord 24:32-9. 2009
    ..These findings extend the clinical and pathological features that may be associated with LRRK2 mutations...
  8. ncbi request reprint Mouse model of multiple system atrophy alpha-synuclein expression in oligodendrocytes causes glial and neuronal degeneration
    Ikuru Yazawa
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Neuron 45:847-59. 2005
    ....
  9. pmc Convergence of heat shock protein 90 with ubiquitin in filamentous alpha-synuclein inclusions of alpha-synucleinopathies
    Kunihiro Uryu
    The Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, Pennsylvania 19104 4283, USA
    Am J Pathol 168:947-61. 2006
    ..These data implicate predominantly Hsp90 in the formation of alpha-syn inclusions in PD and related alpha-synucleinopathies...
  10. pmc Specificity and regulation of casein kinase-mediated phosphorylation of alpha-synuclein
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    J Neuropathol Exp Neurol 67:402-16. 2008
    ..These data provide novel explanations for the presence of hyperphosphorylated Ser129 alpha-syn in pathologic inclusions...
  11. pmc Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies
    Deepak M Sampathu
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Am J Pathol 163:91-100. 2003
    ..These results suggest that ubiquitination of alpha-synuclein is not required for inclusion formation and follows the fibrillization of alpha-synuclein...
  12. pmc E46K human alpha-synuclein transgenic mice develop Lewy-like and tau pathology associated with age-dependent, detrimental motor impairment
    Kristel L Emmer
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 286:35104-18. 2011
    ..Collectively, these findings provide insights in the mechanisms of formation of these aberrant proteinaceous inclusions and support the notion that α-syn aggregates are involved in the pathogenesis of human diseases...
  13. pmc DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function
    Ling Yang Hao
    Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 107:9747-52. 2010
    ..These findings link DJ-1, pink1, and parkin to mitochondrial integrity and provide the foundation for therapeutics that link bioenergetics and parkinsonism...
  14. ncbi request reprint The E46K mutation in alpha-synuclein increases amyloid fibril formation
    Eric A Greenbaum
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 280:7800-7. 2005
    ..These findings support the notion that aberrant alpha-synuclein polymerization resulting in the formation of pathological inclusions can lead to disease...
  15. pmc Leucine-rich repeat kinase 2 expression leads to aggresome formation that is not associated with alpha-synuclein inclusions
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    J Neuropathol Exp Neurol 68:785-96. 2009
    ..Thus, although LRRK2 is a model system for aggresome formation, LRRK2 is not present in alpha-syn pathological inclusions...
  16. pmc Characterization of hydrophobic residue requirements for alpha-synuclein fibrillization
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 48:9427-36. 2009
    ....
  17. pmc L10p and P158DEL DJ-1 mutations cause protein instability, aggregation, and dimerization impairments
    Chenere P Ramsey
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    J Neurosci Res 88:3111-24. 2010
    ..Taken together, these findings suggest that diverse aberrant mechanisms, including alterations in protein stability and protein folding, are associated with the pathogenicity of the L10P and P158DEL DJ-1 variants...
  18. pmc Identification and characterization of a novel endogenous murine parkin mutation
    Chenere P Ramsey
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    J Neurochem 113:402-17. 2010
    ....
  19. ncbi request reprint More than just two peas in a pod: common amyloidogenic properties of tau and alpha-synuclein in neurodegenerative diseases
    Virginia M Y Lee
    The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, and Institute on Aging, The University of Pennsylvania, Philadelphia, PA 19104 4283, USA
    Trends Neurosci 27:129-34. 2004
    ..Thus, the ability of tau and alpha-synuclein to affect each other directly or indirectly might contribute to the overlap in the clinical and pathological features of tauopathies and synucleinopathies...
  20. ncbi request reprint Effects of oxidative and nitrative challenges on alpha-synuclein fibrillogenesis involve distinct mechanisms of protein modifications
    Erin H Norris
    Center for Neurodegenerative Disease Research and the Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 278:27230-40. 2003
    ..These findings demonstrate that nitrative and/or oxidative stress results in distinct mechanisms of alpha-synuclein protein modifications that can influence the formation of stable alpha-synuclein fibrils...
  21. pmc Degradative organelles containing mislocalized alpha-and beta-synuclein proliferate in presenilin-1 null neurons
    Christina A Wilson
    Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA 19104, USA
    J Cell Biol 165:335-46. 2004
    ....
  22. pmc Pesticide exposure exacerbates alpha-synucleinopathy in an A53T transgenic mouse model
    Erin H Norris
    Center for Neurodegenerative Disease Research, Institute on Aging, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3600 Spruce St, Maloney 3, HUP, Philadelphia, PA 19104 4283, USA
    Am J Pathol 170:658-66. 2007
    ..These studies support the notion that environmental factors causing nitrative damage are closely linked to mechanisms underlying the formation of alpha-synuclein pathologies and the onset of Parkinson's-like neurodegeneration...
  23. pmc DJ-1 deficient mice demonstrate similar vulnerability to pathogenic Ala53Thr human alpha-syn toxicity
    Chenere P Ramsey
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Hum Mol Genet 19:1425-37. 2010
    ..It is possible that alpha-syn and DJ-1 mutations may lead to PD via independent mechanisms...
  24. pmc The E163K DJ-1 mutant shows specific antioxidant deficiency
    Chenere P Ramsey
    Department of Pharmacology, University of Pennsylvania School of Medicine, 125 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104 6084, USA
    Brain Res 1239:1-11. 2008
    ..These findings suggest that DJ-1 influences several neuroprotective pathways and that the E163K mutation impairs the mechanism that is more specific to oxidative stress...
  25. ncbi request reprint Fibrillization of alpha-synuclein and tau in familial Parkinson's disease caused by the A53T alpha-synuclein mutation
    Paul T Kotzbauer
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Exp Neurol 187:279-88. 2004
    ..Our data implicate fibrillization of alpha-syn and tau in the pathogenesis of PD, and suggest that distinct amyloidogenic proteins may cross-seed each other in neurodegenerative diseases...
  26. pmc The G2019S pathogenic mutation disrupts sensitivity of leucine-rich repeat kinase 2 to manganese kinase inhibition
    Jason P Covy
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    J Neurochem 115:36-46. 2010
    ..From these findings, a new model is proposed for a possible function of LRRK2 and the consequence of the G2019S LRRK2 pathogenic mutation...
  27. ncbi request reprint Tau and 14-3-3 in glial cytoplasmic inclusions of multiple system atrophy
    Benoit I Giasson
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3rd Floor Maloney Building, Philadelphia, PA 19104, USA
    Acta Neuropathol 106:243-50. 2003
    ....
  28. ncbi request reprint Role of alpha-synuclein carboxy-terminus on fibril formation in vitro
    Ian V J Murray
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 42:8530-40. 2003
    ..Thus, the carboxy-terminus of alpha-syn may regulate aggregation of full-length alpha-syn and determine the diameter of alpha-syn filaments...
  29. ncbi request reprint Distinct cleavage patterns of normal and pathologic forms of alpha-synuclein by calpain I in vitro
    Amanda J Mishizen-Eberz
    Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Neurochem 86:836-47. 2003
    ..Elucidating the role of calpain I in the proteolytic processing of alpha-syn in normal and diseased brains may clarify mechanisms of neurodegenerative alpha-synucleinopathies...
  30. ncbi request reprint Novel monoclonal antibodies demonstrate biochemical variation of brain parkin with age
    Aaron C Pawlyk
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 278:48120-8. 2003
    ....
  31. pmc Nitration of tau protein is linked to neurodegeneration in tauopathies
    Takashi Horiguchi
    Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 4283, USA
    Am J Pathol 163:1021-31. 2003
    ..Taken together, these findings imply that nitrative injury is directly linked to the formation of filamentous tau inclusions...
  32. ncbi request reprint A comparison of amyloid fibrillogenesis using the novel fluorescent compound K114
    Adam S Crystal
    The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Neurochem 86:1359-68. 2003
    ....
  33. ncbi request reprint Role of oxidative damage in protein aggregation associated with Parkinson's disease and related disorders
    Erin H Norris
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Antioxid Redox Signal 7:672-84. 2005
    ..Differences in the level, type, and temporal sequence of the oxidative alterations appear to result in both inhibitory and stimulatory effects on the fibrillogenesis of these proteins...
  34. ncbi request reprint Interactions of amyloidogenic proteins
    Benoit I Giasson
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 4283, USA
    Neuromolecular Med 4:49-58. 2003
    ..These results indicate that the formation of amyloid composed of different proteins can affect each other directly or indirectly, likely contributing to the overlap in clinical and pathological features...
  35. pmc A novel, high-efficiency cellular model of fibrillar alpha-synuclein inclusions and the examination of mutations that inhibit amyloid formation
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    J Neurochem 113:374-88. 2010
    ..This novel high-efficiency cellular model of alpha-syn aggregation is a valuable system that may be used to further understand alpha-syn aggregation and allow for the generation of future therapeutics...
  36. pmc Characterization of antibodies that selectively detect alpha-synuclein in pathological inclusions
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 123 John Morgan Building, Philadelphia, PA, 19104, USA
    Acta Neuropathol 116:37-46. 2008
    ....
  37. ncbi request reprint Alpha-synuclein: normal function and role in neurodegenerative diseases
    Erin H Norris
    Center for Neurodegenerative Disease Research and the Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Curr Top Dev Biol 60:17-54. 2004
    ..Therefore, research must be continued in order to better understand the functions of the synuclein proteins under normal physiological conditions as well as their role in diseases...
  38. pmc α-Synuclein, leucine-rich repeat kinase-2, and manganese in the pathogenesis of Parkinson disease
    Jason P Covy
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6084, USA
    Neurotoxicology 32:622-9. 2011
    ....
  39. pmc Studies of protein aggregation in A53T α-synuclein transgenic, Tg2576 transgenic, and P246L presenilin-1 knock-in cross bred mice
    Kristel L Emmer
    Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 6084, USA
    Neurosci Lett 507:137-42. 2012
    ..These studies show that Aβ amyloid deposits can cause the local aggregation of α-syn, but these did not lead to more extensive α-syn pathology...
  40. ncbi request reprint Are ubiquitination pathways central to Parkinson's disease?
    Benoit I Giasson
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 114:1-8. 2003
    ....
  41. pmc Induction of intracellular tau aggregation is promoted by α-synuclein seeds and provides novel insights into the hyperphosphorylation of tau
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6084, USA
    J Neurosci 31:7604-18. 2011
    ..The current work not only provides an exceptional cellular model of tau pathology, but also examines α-syn-induced tau inclusion formation and provides novel insights into hyperphosphorylation observed in disease...
  42. ncbi request reprint Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases
    John E Duda
    Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Ann Neurol 52:205-10. 2002
    ....
  43. pmc Residue Glu83 plays a major role in negatively regulating alpha-synuclein amyloid formation
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
    Biochem Biophys Res Commun 391:1415-20. 2010
    ....
  44. doi request reprint Characterization of kinases involved in the phosphorylation of aggregated α-synuclein
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    J Neurosci Res 89:231-47. 2011
    ....
  45. pmc Identification of compounds that inhibit the kinase activity of leucine-rich repeat kinase 2
    Jason P Covy
    Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
    Biochem Biophys Res Commun 378:473-7. 2009
    ..These findings provide important insights and tools to study the mechanisms of LRRK2 pathobiology, and could lead to therapeutic applications...
  46. ncbi request reprint Snaring the function of alpha-synuclein
    Nancy M Bonini
    Department of Biology and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cell 123:359-61. 2005
    ..These proteins are crucial for release of neurotransmitters at the neuronal synapse, vesicle recycling, and synaptic integrity...
  47. pmc Molecular mechanisms of alpha-synuclein neurodegeneration
    Elisa A Waxman
    Department of Pharmacology, University of Pennsylvania School of Medicine, 125 John Morgan Building, Philadelphia, PA 19104 6084, USA
    Biochim Biophys Acta 1792:616-24. 2009
    ..In this review, some of the evidence for the different mechanisms of alpha-synuclein toxicity is presented and discussed...
  48. ncbi request reprint Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein
    Benoit I Giasson
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, 3600 Spruce Street, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Neuron 34:521-33. 2002
    ..These mice demonstrate that A53T alpha-synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal inclusions that cause neurodegeneration...
  49. ncbi request reprint Gamma-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathways
    Zhong Zong Pan
    Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 277:35050-60. 2002
    ....
  50. ncbi request reprint Role of mitochondrial dysfunction in Parkinson's disease: Implications for treatment
    Chenere P Ramsey
    Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6084, USA
    Drugs Aging 24:95-105. 2007
    ....
  51. ncbi request reprint The environmental toxin arsenite induces tau hyperphosphorylation
    Benoit I Giasson
    University of Pennsylvania School of Medicine, Third Floor Maloney Building, 3600 Spruce Street, Philadelphia, Pennsylvania 19104, USA
    Biochemistry 41:15376-87. 2002
    ....
  52. ncbi request reprint The relationship between oxidative/nitrative stress and pathological inclusions in Alzheimer's and Parkinson's diseases
    Benoit I Giasson
    Center for Neurodegenerative Disease Research and Department of Pathology and Laboratory Medicine, The University of Pennsylvania, Philadelphia, PA 19104 4283, USA
    Free Radic Biol Med 32:1264-75. 2002
    ..It can be surmised that oxidative/nitrative stress, which is cooperatively influenced by environmental factors, genetic predisposition, and senescence, may be a link between these disorders...
  53. ncbi request reprint DJ-1 is present in a large molecular complex in human brain tissue and interacts with alpha-synuclein
    Marc C Meulener
    Department of Biology and Laboratory of Medicine of University of Pennsylvania, Philadelphia 19104 6084, USA
    J Neurochem 93:1524-32. 2005
    ..Furthermore, our results provide further evidence for the interplay between neurodegenerative disease-associated proteins...
  54. ncbi request reprint Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred
    John E Duda
    Parkinson s Disease Research, Education and Clinical Center, Philadelphia Veterans Affairs Medical Center, Pennsylvania, USA
    Acta Neuropathol 104:7-11. 2002
    ..We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in alpha-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brains...
  55. ncbi request reprint Initiation and synergistic fibrillization of tau and alpha-synuclein
    Benoit I Giasson
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine
    Science 300:636-40. 2003
    ..This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases...
  56. pmc Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies
    Manuela Neumann
    Department of Neuropathology, Ludwig Maximilians University, Munich, Germany
    J Clin Invest 110:1429-39. 2002
    ..The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions...
  57. 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...
  58. ncbi request reprint Functional consequences of alpha-synuclein tyrosine nitration: diminished binding to lipid vesicles and increased fibril formation
    Roberto Hodara
    Stokes Research Institute and Department of Biochemistry and Biophysics, Children s Hospital of Philadelphia and The University of Pennsylvania, 19104, USA
    J Biol Chem 279:47746-53. 2004
    ..Collectively, these data suggest that post-translational modification of alpha-syn by nitration can promote the formation of intracytoplasmic inclusions that constitute the hallmark of Parkinson disease and other synucleinopathies...
  59. ncbi request reprint A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: implications for pathogenesis of Parkinson disease
    Chang wei Liu
    Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 75390, USA
    J Biol Chem 280:22670-8. 2005
    ..This model has parallels in other neurodegenerative diseases, such as Huntington disease, where coaggregation of poly(Q) fragments with full-length protein has been observed...