K Iqbal

Summary

Country: USA

Publications

  1. ncbi Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity
    Alejandra del C Alonso
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    Proc Natl Acad Sci U S A 103:8864-9. 2006
  2. ncbi Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective
    Khalid Iqbal
    New York State Institute for Basic Research, in Developmental Disabilities, Department of Neurochemistry, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    J Alzheimers Dis 9:219-42. 2006
  3. ncbi Mechanisms of tau-induced neurodegeneration
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA
    Acta Neuropathol 118:53-69. 2009
  4. ncbi Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention
    K Iqbal
    Department of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities, Forest Hill Road, Staten Island, New York, NY 10314, USA
    J Cell Mol Med 12:38-55. 2008
  5. ncbi Alzheimer neurofibrillary degeneration: therapeutic targets and high-throughput assays
    Khalid Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 6399, USA
    J Mol Neurosci 20:425-9. 2003
  6. ncbi From tangles to tau protein
    K Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA
    Bratisl Lek Listy 107:341-2. 2006
  7. ncbi Metabolic/signal transduction hypothesis of Alzheimer's disease and other tauopathies
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, 10314 6399, USA
    Acta Neuropathol 109:25-31. 2005
  8. ncbi Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers
    Khalid Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    Ann Neurol 58:748-57. 2005
  9. ncbi Inhibition of neurofibrillary degeneration: a promising approach to Alzheimer's disease and other tauopathies
    K Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    Curr Drug Targets 5:495-502. 2004
  10. ncbi Developing pharmacological therapies for Alzheimer disease
    K Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA
    Cell Mol Life Sci 64:2234-44. 2007

Collaborators

Detail Information

Publications94

  1. ncbi Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity
    Alejandra del C Alonso
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    Proc Natl Acad Sci U S A 103:8864-9. 2006
    ....
  2. ncbi Discoveries of tau, abnormally hyperphosphorylated tau and others of neurofibrillary degeneration: a personal historical perspective
    Khalid Iqbal
    New York State Institute for Basic Research, in Developmental Disabilities, Department of Neurochemistry, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    J Alzheimers Dis 9:219-42. 2006
    ....
  3. ncbi Mechanisms of tau-induced neurodegeneration
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA
    Acta Neuropathol 118:53-69. 2009
    ..AD is multifactorial and heterogeneous and involves more than one etiopathogenic mechanism...
  4. ncbi Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention
    K Iqbal
    Department of Neurochemistry New York State Institute for Basic Research in Developmental Disabilities, Forest Hill Road, Staten Island, New York, NY 10314, USA
    J Cell Mol Med 12:38-55. 2008
    ..The AD subgroup identification of patients can help increase the success of clinical trials and the development of specific and potent disease modifying drugs...
  5. ncbi Alzheimer neurofibrillary degeneration: therapeutic targets and high-throughput assays
    Khalid Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 6399, USA
    J Mol Neurosci 20:425-9. 2003
    ..Development of high-throughput screening assays for potential drugs aimed at these therapeutic targets is currently under way...
  6. ncbi From tangles to tau protein
    K Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA
    Bratisl Lek Listy 107:341-2. 2006
    ..Finally, after one hundred years the exact nature of the neurofibrillary tangles and their role in neurodegeneration is beginning to be unraveled...
  7. ncbi Metabolic/signal transduction hypothesis of Alzheimer's disease and other tauopathies
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, 10314 6399, USA
    Acta Neuropathol 109:25-31. 2005
    ..The hyperphosphorylated tau sequesters normal tau, MAP1 and MAP2, which results in breakdown of the microtubule network and, consequently, a progressive retrograde degeneration of the affected neurons and, ultimately, dementia...
  8. ncbi Subgroups of Alzheimer's disease based on cerebrospinal fluid molecular markers
    Khalid Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    Ann Neurol 58:748-57. 2005
    ..These subgroups, which can be identified by CSF analysis, might benefit differently from different therapeutic drugs...
  9. ncbi Inhibition of neurofibrillary degeneration: a promising approach to Alzheimer's disease and other tauopathies
    K Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    Curr Drug Targets 5:495-502. 2004
    ..Thus, the development of drugs that inhibit neurofibrillary degeneration is a very promising and feasible therapeutic approach to AD and related tauopathies...
  10. ncbi Developing pharmacological therapies for Alzheimer disease
    K Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA
    Cell Mol Life Sci 64:2234-44. 2007
    ..Restoration of the phosphatase activity which is downregulated in AD brain or inhibition of GSK-3beta and cdk5, which are required for AD-type abnormal hyperphosphorylation of tau, are among the most promising therapeutic strategies...
  11. ncbi Cytosolic abnormally hyperphosphorylated tau but not paired helical filaments sequester normal MAPs and inhibit microtubule assembly
    Khalid Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314 6399, USA
    J Alzheimers Dis 14:365-70. 2008
    ..These findings suggest the inhibition of tau abnormal hyperphosphorylation and not the aggregation of tau as the preferred therapeutic target for AD and related tauopathies...
  12. ncbi Tau pathology in Alzheimer disease and other tauopathies
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    Biochim Biophys Acta 1739:198-210. 2005
    ..Inhibition of this tau abnormality is one of the most promising therapeutic approaches to AD and other tauopathies...
  13. ncbi Tau is phosphorylated by GSK-3 at several sites found in Alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by A-kinase
    J Z Wang
    Chemical Neuropathology Department, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314 6399, USA
    FEBS Lett 436:28-34. 1998
    ..Thus a combined role of A-kinase and GSK-3 should be considered in Alzheimer neurofibrillary degeneration...
  14. ncbi Phosphorylation of microtubule-associated protein tau is regulated by protein phosphatase 2A in mammalian brain. Implications for neurofibrillary degeneration in Alzheimer's disease
    C X Gong
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 6399, USA
    J Biol Chem 275:5535-44. 2000
    ..A down-regulation of protein phosphatase 2A activity can lead to Alzheimer-like abnormal hyperphosphorylation of tau...
  15. ncbi Aberrant glycosylation modulates phosphorylation of tau by protein kinase A and dephosphorylation of tau by protein phosphatase 2A and 5
    F Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    Neuroscience 115:829-37. 2002
    ..The combined impact of this modulation may be to make tau more susceptible to becoming abnormally hyperphosphorylated...
  16. ncbi Mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach
    K Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA
    J Neural Transm Suppl 59:213-22. 2000
    ..e. PHF/SF. Increase in tau phosphatase activity is a promising approach to inhibit neurofibrillary degeneration and thereby the diseases characterized by this lesion...
  17. ncbi Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments
    A Alonso
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    Proc Natl Acad Sci U S A 98:6923-8. 2001
    ....
  18. ncbi Interaction of tau isoforms with Alzheimer's disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein
    A D Alonso
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Biol Chem 276:37967-73. 2001
    ..Thus, lack of amino-terminal inserts and extra microtubule binding domain repeat in fetal human brain might be protective from Alzheimer's neurofibrillary degeneration...
  19. ncbi Tau in Alzheimer disease and related tauopathies
    K Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    Curr Alzheimer Res 7:656-64. 2010
    ..Inhibition of abnormal hyperphosphorylation of tau offers a promising therapeutic target for AD and related tauopathies...
  20. ncbi Metabolically active rat brain slices as a model to study the regulation of protein phosphorylation in mammalian brain
    C X Gong
    New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    Brain Res Brain Res Protoc 6:134-40. 2001
    ..Furthermore, unlike cultured cells, the neurons in the brain slices reside in the physiological environment of the brain consisting of natural extracellular matrix, neuronal connectivity, and neuronal-glial interactions...
  21. ncbi Post-translational modifications of tau protein in Alzheimer's disease
    C X Gong
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    J Neural Transm 112:813-38. 2005
    ..Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies...
  22. ncbi Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease
    C X Gong
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA
    Curr Med Chem 15:2321-8. 2008
    ..Development of drugs on the basis of these strategies is likely to lead to disease-modifying therapies for AD...
  23. ncbi Memantine inhibits and reverses the Alzheimer type abnormal hyperphosphorylation of tau and associated neurodegeneration
    Liang Li
    Department of Neurochemistry, NYS Institute for Basic Research, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA
    FEBS Lett 566:261-9. 2004
    ....
  24. ncbi PP2B isolated from human brain preferentially dephosphorylates Ser-262 and Ser-396 of the Alzheimer disease abnormally hyperphosphorylated tau
    A Rahman
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
    J Neural Transm 113:219-30. 2006
    ..The preferential dephosphorylation of Ser262 and Ser396 by PP2B suggests a possible involvement of this phosphatase in Alzheimer neurofibrillary degeneration...
  25. ncbi Multiple forms of phosphatase from human brain: isolation and partial characterization of affi-gel blue nonbinding phosphatase activities
    L Y Cheng
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA
    Neurochem Res 26:425-38. 2001
    ..The resulting dephosphorylated tau regained its activity in promoting the microtubule assembly, suggesting that P7-P11 might regulate the phosphorylation of tau protein in the brain...
  26. ncbi Significance and mechanism of Alzheimer neurofibrillary degeneration and therapeutic targets to inhibit this lesion
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314 6399, USA
    J Mol Neurosci 19:95-9. 2002
    ....
  27. ncbi Disruption of microtubule network by Alzheimer abnormally hyperphosphorylated tau
    Bin Li
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    Acta Neuropathol 113:501-11. 2007
    ..This study, for the first time, provides direct mechanistic insights into the molecular basis of both axonal and dendritic neurodegeneration seen in Alzheimer disease...
  28. ncbi Regulation of phosphorylation of tau by protein kinases in rat brain
    Amitabha Sengupta
    Department of Neurochemistry, New York State Institute for Basic Research, Staten Island, NY 10314-6399, USA
    Neurochem Res 31:1473-80. 2006
    ....
  29. ncbi Phosphorylation of tau at both Thr 231 and Ser 262 is required for maximal inhibition of its binding to microtubules
    A Sengupta
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island 10314, USA
    Arch Biochem Biophys 357:299-309. 1998
    ..Together, our results indicate that the binding of tau to microtubules is controlled by the phosphorylation of several sites, among which are Thr 231, Ser 235, and Ser 262...
  30. ncbi Biological markers in Alzheimer's disease
    I Grundke-Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    Bratisl Lek Listy 107:359-65. 2006
    ..Identification of various subgroups of AD will help improvement in diagnoses and development of potent therapeutic drugs (Tab. 2, Fig. 2, Ref. 53)...
  31. ncbi Phosphothreonine-212 of Alzheimer abnormally hyperphosphorylated tau is a preferred substrate of protein phosphatase-1
    Abdur Rahman
    Department of Neurochemistry, New York Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    Neurochem Res 30:277-87. 2005
    ..Of the sites dephosphorylated, pT212 was only a substrate for PP1, as purified/enriched PP2A and PP2B from the same brains did not dephosphorylate this site...
  32. ncbi Hyperphosphorylation-induced self assembly of murine tau: a comparison with human tau
    M O Chohan
    Department of Neurochemistry, NYS Institute for Basic Research, Staten Island, NY 10314, USA
    J Neural Transm 112:1035-47. 2005
    ..The filaments obtained from self assembly of murine tau closely resembled those formed from identically treated human tau. Moreover, like human tau, 60-70% of murine tau aggregated on hyperphosphorylation...
  33. ncbi Neurofibrillary pathology leads to synaptic loss and not the other way around in Alzheimer disease
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA
    J Alzheimers Dis 4:235-8. 2002
  34. ncbi Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA
    Eur J Neurosci 22:1942-50. 2005
    ..Our findings indicate that PP2A is the major tau phosphatase that regulates its phosphorylation at multiple sites in human brain. The abnormal hyperphosphorylation of tau is partially due to a downregulation of PP2A activity in AD brain...
  35. ncbi Pharmacological approaches of neurofibrillary degeneration
    Khalid Iqbal
    NYS Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, 10314 USA. att.net
    Curr Alzheimer Res 2:335-41. 2005
    ..The development of drugs that inhibit neurofibrillary degeneration is a very promising and feasible therapeutic approach to inhibit the progression of AD and related tauopathies...
  36. ncbi Alzheimer's disease neurofibrillary degeneration: pivotal and multifactorial
    Khalid Iqbal
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA
    Biochem Soc Trans 38:962-6. 2010
    ..Restoration of PP2A activity by inhibition of the cleavage of I(2)(PP2A)/SET offers a promising therapeutic opportunity in AD with this aetiopathogenic mechanism...
  37. ncbi Tau-induced neurodegeneration: a clue to its mechanism
    Alejandra del C Alonso
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314-6399, USA
    J Alzheimers Dis 8:223-6. 2005
  38. ncbi Decrease of protein phosphatase 2A and its association with accumulation and hyperphosphorylation of tau in Down syndrome
    Zhihou Liang
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 6399, USA
    J Alzheimers Dis 13:295-302. 2008
    ..Our results indicate that PP2A is down-regulated in DS brain and suggest that this down-regulation might be involved in the abnormal hyperphosphorylation and accumulation of tau...
  39. ncbi Alzheimer's disease, a multifactorial disorder seeking multitherapies
    Khalid Iqbal
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
    Alzheimers Dement 6:420-4. 2010
    ..Levels of disease markers in the cerebrospinal fluid are promising, both in identifying various subgroups of AD and in monitoring the response to therapeutic drugs...
  40. ncbi Overexpression of Dyrk1A contributes to neurofibrillary degeneration in Down syndrome
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Rd, Staten Island, New York 10314, USA
    FASEB J 22:3224-33. 2008
    ..These findings strongly suggest a novel mechanism by which the overexpression of Dyrk1A in DS brain causes neurofibrillary degeneration via hyperphosphorylating tau...
  41. ncbi Impaired brain glucose metabolism leads to Alzheimer neurofibrillary degeneration through a decrease in tau O-GlcNAcylation
    Cheng Xin Gong
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    J Alzheimers Dis 9:1-12. 2006
    ..Further studies of this mechanism are likely to offer a novel therapeutic target for preventing and treating AD...
  42. ncbi Up-regulation of inhibitors of protein phosphatase-2A in Alzheimer's disease
    Hitoshi Tanimukai
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314-6399, USA
    Am J Pathol 166:1761-71. 2005
    ..These studies suggest the possible involvement of I1(PP2A) and I2(PP2A) in the abnormal hyperphosphorylation of tau in AD...
  43. ncbi Inhibitors of protein phosphatase-2A from human brain structures, immunocytological localization and activities towards dephosphorylation of the Alzheimer type hyperphosphorylated tau
    Ichiro Tsujio
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 6399, USA
    FEBS Lett 579:363-72. 2005
    ..Overexpression of I(1)(PP2A) as well as I(2)(PP2A) results in tau hyperphosphorylation and degeneration of PC 12 cells...
  44. ncbi Targeting tau protein in Alzheimer's disease
    Cheng Xin Gong
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    Drugs Aging 27:351-65. 2010
    ....
  45. ncbi Dephosphorylation of microtubule-associated protein tau by protein phosphatase 5
    Cheng Xin Gong
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Neurochem 88:298-310. 2004
    ..These results suggest that PP5 plays a role in the dephosphorylation of tau and might be involved in the molecular pathogenesis of Alzheimer's disease...
  46. ncbi Promotion of hyperphosphorylation by frontotemporal dementia tau mutations
    Alejandra del C Alonso
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314-6399, USA
    J Biol Chem 279:34873-81. 2004
    ..These findings taken together suggest that the mutations in tau might cause neurodegeneration by making the protein a more favorable substrate for hyperphosphorylation...
  47. ncbi The dentate gyrus neurogenesis: a therapeutic target for Alzheimer's disease
    Yoshitaka Tatebayashi
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314, USA
    Acta Neuropathol (Berl) 105:225-32. 2003
    ....
  48. ncbi Regulation of microtubule-associated proteins, protein kinases and protein phosphatases during differentiation of SY5Y cells
    Niloufar Haque
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA
    Brain Res Mol Brain Res 129:163-70. 2004
    ..These results suggest that the expression, post-translational modifications and biological activities of various MAPs are differentially regulated to meet the biological needs during cell differentiation...
  49. ncbi Role of glycosylation in hyperphosphorylation of tau in Alzheimer's disease
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    FEBS Lett 512:101-6. 2002
    ..These results suggest that the glycosylation of tau is an early abnormality that can facilitate the subsequent abnormal hyperphosphorylation of tau in AD brain...
  50. ncbi Dephosphorylation of tau by protein phosphatase 5: impairment in Alzheimer's disease
    Fei Liu
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Biol Chem 280:1790-6. 2005
    ..These results suggest that tau is probably a physiological substrate of PP5 and that the abnormal hyperphosphorylation of tau in AD might result in part from the decreased PP5 activity in the diseased brains...
  51. ncbi Anesthesia induces phosphorylation of tau
    Xiaoqin Run
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314 6399, USA
    J Alzheimers Dis 16:619-26. 2009
    ..Our findings also provide a possible mechanism by which anesthesia may cause postoperative cognitive impairment and increase the risk for AD...
  52. ncbi Dysregulation of insulin signaling, glucose transporters, O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain: Implication for Alzheimer's disease
    Yanqiu Deng
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314, USA
    Am J Pathol 175:2089-98. 2009
    ....
  53. ncbi Involvement of aberrant glycosylation in phosphorylation of tau by cdk5 and GSK-3beta
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island 10314, USA
    FEBS Lett 530:209-14. 2002
    ..These data suggest that aberrant glycosylation of tau in AD might be involved in neurofibrillary degeneration by promoting abnormal hyperphosphorylation by cdk5 and GSK-3beta...
  54. ncbi Decreased glucose transporters correlate to abnormal hyperphosphorylation of tau in Alzheimer disease
    Ying Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    FEBS Lett 582:359-64. 2008
    ....
  55. ncbi Inhibition of protein phosphatase 2A induces phosphorylation and accumulation of neurofilaments in metabolically active rat brain slices
    Cheng-Xin Gong
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA
    Neurosci Lett 340:107-10. 2003
    ..These findings suggest that the hyperphosphorylation and accumulation of NF found in AD brain could have been caused by the down-regulation of PP2A...
  56. ncbi The carboxy-terminal fragment of inhibitor-2 of protein phosphatase-2A induces Alzheimer disease pathology and cognitive impairment
    Xiaochuan Wang
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA
    FASEB J 24:4420-32. 2010
    ..These findings suggest a novel etiopathogenic mechanism of AD, which is initiated by the cleavage of I(2)(PP2A), producing I(2CTF), and describe a novel disease-relevant nontransgenic animal model of AD...
  57. ncbi Tau in cerebrospinal fluid: a sensitive sandwich enzyme-linked immunosorbent assay using tyramide signal amplification
    Hidenaga Yamamori
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
    Neurosci Lett 418:186-9. 2007
    ..A highly significant correlation was found between this assay and a commonly used kit, INNOTEST hTAU Antigen...
  58. ncbi Involvement of I2PP2A in the abnormal hyperphosphorylation of tau and its reversal by Memantine
    Muhammad Omar Chohan
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA
    FEBS Lett 580:3973-9. 2006
    ..These findings demonstrate novel mechanisms by which I2PP2A regulates the intracellular activity of PP2A and phosphorylation of tau, and by which Memantine modulates PP2A signaling and inhibits neurofibrillary degeneration...
  59. ncbi Developmental regulation of tau phosphorylation, tau kinases, and tau phosphatases
    Yang Yu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA
    J Neurochem 108:1480-94. 2009
    ..These studies provide new insight into the developmental regulation of site-specific tau phosphorylation and identify the likely sites required for the abnormal hyperphosphorylation of tau in AD...
  60. ncbi Regulation of phosphorylation of tau by cyclin-dependent kinase 5 and glycogen synthase kinase-3 at substrate level
    Amitabha Sengupta
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    FEBS Lett 580:5925-33. 2006
    ..These findings suggest that the phosphorylation of tau at Thr231 and Ser262 by cdk5 plus GSK-3, which inhibits its normal biological activity, is regulated both by its amino terminal inserts and its physical state...
  61. ncbi Mechanism of tau-induced neurodegeneration in Alzheimer disease and related tauopathies
    Alejandra del C Alonso
    Department of Biology and Center for Developmental Neuroscience and Developmental Disabilities, College of Staten Island, The City University of New York, Staten Island, NY 10314, USA
    Curr Alzheimer Res 5:375-84. 2008
    ..Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration...
  62. ncbi Site-specific effects of tau phosphorylation on its microtubule assembly activity and self-aggregation
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    Eur J Neurosci 26:3429-36. 2007
    ..These studies reveal the differential regulation of tau's biological activity and self-aggregation by phosphorylation at various sites/regions...
  63. ncbi O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    Proc Natl Acad Sci U S A 101:10804-9. 2004
    ....
  64. ncbi Reduced O-GlcNAcylation links lower brain glucose metabolism and tau pathology in Alzheimer's disease
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    Brain 132:1820-32. 2009
    ..Thus, restoration of brain tau O-GlcNAcylation and protein phosphatase 2A activity may offer promising therapeutic targets for treating Alzheimer's disease...
  65. ncbi Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer's disease
    Ying Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA
    J Neurochem 111:242-9. 2009
    ..These results suggest that T2DM may contribute to the increased risk for AD by impairing brain glucose uptake/metabolism and, consequently, down-regulation of O-GlcNAcylation, which facilitates abnormal hyperphosphorylation of tau...
  66. ncbi Dysregulation of tau phosphorylation in mouse brain during excitotoxic damage
    Zhihou Liang
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314 6399, USA
    J Alzheimers Dis 17:531-9. 2009
    ....
  67. ncbi I1PP2A affects tau phosphorylation via association with the catalytic subunit of protein phosphatase 2A
    She Chen
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Biol Chem 283:10513-21. 2008
    ..Double immunofluorescence staining showed that I (1)(PP2A) and I (1)(PP2A)DeltaC2 increased Tau phosphorylation and impaired the microtubule network and neurite outgrowth in PC12 cells treated with nerve growth factor...
  68. ncbi Failure of neuronal maturation in Alzheimer disease dentate gyrus
    Bin Li
    Department of Neurochemistry, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA
    J Neuropathol Exp Neurol 67:78-84. 2008
    ..These findings suggest that newly generated neurons in Alzheimer disease dentate gyrus do not become mature neurons, although neuroproliferation is increased...
  69. ncbi Phosphorylation of tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration
    Alejandra D Alonso
    Department of Biology and Center for Developmental Neuroscience, College of Staten Island, and The Graduate Center, The City University of New York, New York 10314, USA
    J Biol Chem 285:30851-60. 2010
    ..Cells transfected with pseudophosphorylated Tau became TUNEL-positive...
  70. ncbi Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain
    Zhihou Liang
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, USA
    J Neurochem 103:2462-70. 2007
    ....
  71. ncbi Role of tau phosphorylation by glycogen synthase kinase-3beta in the regulation of organelle transport
    Yoshitaka Tatebayashi
    New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA
    J Cell Sci 117:1653-63. 2004
    ..These findings raise the possibility that the phosphorylation of tau by glycogen synthase kinase-3 might be involved in the regulation of organelle transport...
  72. ncbi NF-kappaB precursor, p105, and NF-kappaB inhibitor, IkappaBgamma, are both elevated in Alzheimer disease brain
    Yu Huang
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314-6399, USA
    Neurosci Lett 373:115-8. 2005
    ..Our findings suggest that the NF-kappaB pathway might be involved in the molecular mechanism of AD...
  73. ncbi Inhibitors of protein phosphatase-2A: topography and subcellular localization
    Hitoshi Tanimukai
    New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314, USA
    Brain Res Mol Brain Res 126:146-56. 2004
    ..These studies suggest that PP-2A activity is probably regulated by I1(PP2A) and I2(PP2A) in the adult mammalian central nervous system, and that these inhibitors are conserved between rat and human brains...
  74. ncbi From tau to toxicity: emerging roles of NMDA receptor in Alzheimer's disease
    Muhammad Omar Chohan
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    J Alzheimers Dis 10:81-7. 2006
    ..Here, we analyze some of the most intriguing evidence for NMDA receptor-mediated cellular dysfunction and propose a mechanism by which hyperactive NMDA receptors might lead to neurofibrillary degeneration in Alzheimer's disease...
  75. ncbi PKA modulates GSK-3beta- and cdk5-catalyzed phosphorylation of tau in site- and kinase-specific manners
    Fei Liu
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA
    FEBS Lett 580:6269-74. 2006
    ..These studies reveal the nature of the inter-regulation of tau phosphorylation by the three major tau kinases...
  76. ncbi Regulation between O-GlcNAcylation and phosphorylation of neurofilament-M and their dysregulation in Alzheimer disease
    Yanqiu Deng
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Rd, Staten Island, NY 10314, USA
    FASEB J 22:138-45. 2008
    ....
  77. ncbi Cerebrospinal fluid secretory Ca2+-dependent phospholipase A2 activity is increased in Alzheimer disease
    Sonia Chalbot
    New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314 6399, USA
    Clin Chem 55:2171-9. 2009
    ....
  78. ncbi Elevation of the level and activity of acid ceramidase in Alzheimer's disease brain
    Yu Huang
    Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York 10314 6399, USA
    Eur J Neurosci 20:3489-97. 2004
    ..Our findings suggest that AC might play a role in controlling neuronal apoptosis and that AC-mediated signalling pathways might be involved in the molecular mechanism of AD...
  79. ncbi Levels of nonphosphorylated and phosphorylated tau in cerebrospinal fluid of Alzheimer's disease patients : an ultrasensitive bienzyme-substrate-recycle enzyme-linked immunosorbent assay
    Yuan Yuan Hu
    Pathophysiology Department, Institute forNeuroscience, Tongji Medical School, Huazhong University of Science andTechnology, Wuhan, People's Republic of China
    Am J Pathol 160:1269-78. 2002
    ..It is suggested that the CSF level of tau phosphorylated at Ser-396/Ser-404 is a promising diagnostic marker of AD...
  80. ncbi Okadaic-acid-induced inhibition of protein phosphatase 2A produces activation of mitogen-activated protein kinases ERK1/2, MEK1/2, and p70 S6, similar to that in Alzheimer's disease
    Jin-Jing Pei
    Division of Experimental Geriatrics, Karolinska Institutet, Neurotec, Huddinge, Sweden
    Am J Pathol 163:845-58. 2003
    ....
  81. ncbi Role of protein kinase B in Alzheimer's neurofibrillary pathology
    Jin Jing Pei
    Neurotec, Section for Experimental Geriatrics, Novum, Karolinska Institutet, KFC Plan 4, 141 86 Huddinge, Sweden
    Acta Neuropathol 105:381-92. 2003
    ..These studies suggest the involvement of PKB/GSK-3 signaling in Alzheimer neurofibrillary degeneration...
  82. ncbi In vitro analysis of tau phosphorylation sites and its biological activity
    Jianzhi Wang
    Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan 430030
    Chin Med Sci J 17:13-6. 2002
    ..CONCLUSION: Phosphorylation of tau by PKA plus GSK-3 at Thr-205 might play a key role in tau pathology in AD...
  83. ncbi Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease
    Jin Jing Pei
    Karolinska Institutet, Neurotec, Division of Experimental Geriatrics, Novum, KFC Plan 4, Novum, S 141 86, Huddinge, Sweden
    Brain Res Mol Brain Res 109:45-55. 2002
    ..These data provide direct in situ evidence consistent with the possible involvement of MAP kinase pathway in the hyperphosphorylation of tau and the presence of this lesion before deposition of beta-amyloid in AD...
  84. ncbi Up-regulation of phosphorylated/activated p70 S6 kinase and its relationship to neurofibrillary pathology in Alzheimer's disease
    Wen Lin An
    Division of Experimental Geriatrics, Karolinska Institutet, Neurotec, Novum, Huddinge, Sweden
    Am J Pathol 163:591-607. 2003
    ..A p70 S6 kinase modulated up-regulation of tau translation might contribute to PHF-tau accumulation in neurons with neurofibrillary changes...
  85. ncbi Elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of Alzheimer disease patients
    Yuan-Yuan Hu
    Tongji Medical College, HUST, Wuhan 430030, PR China
    Neurosci Lett 320:156-60. 2002
    ....
  86. ncbi X-ray structure of the PHF core C-terminus: insight into the folding of the intrinsically disordered protein tau in Alzheimer's disease
    Jozef Sevcik
    Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia
    FEBS Lett 581:5872-8. 2007
    ....
  87. ncbi Kinases and phosphatases and tau sites involved in Alzheimer neurofibrillary degeneration
    Jian Zhi Wang
    Pathophysiology Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan P R China
    Eur J Neurosci 25:59-68. 2007
    ..These findings suggest that activation of PP-2A or inhibition of either both GSK-3beta and cdk5 or one of these two kinases plus PKA or CaMKII might be required to inhibit Alzheimer neurofibrillary degeneration...
  88. ncbi Assessments of the accumulation severities of amyloid beta-protein and hyperphosphorylated tau in the medial temporal cortex of control and Alzheimer's brains
    Xin-wen Zhou
    Karolinska Institutet, Department of Neurotec, Geriatric-lab, Novum Plan 5, S-14157, Huddinge, Sweden
    Neurobiol Dis 22:657-68. 2006
    ..Assessments of levels of these abnormal proteins by dot blots may serve as a useful complement to the morphological evaluations in diagnosis of AD...
  89. ncbi Paired helical filaments (PHFs) are a family of single filament structures with a common helical turn period: negatively stained PHF imaged by TEM and measured before and after sonication, deglycosylation, and dephosphorylation
    George C Ruben
    Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA
    Microsc Res Tech 67:175-95. 2005
    ..5-0.6 nm and 0.7-1.0 nm, respectively, and the right-hand helicity of the PHF was lost after deglycosylation. Dephosphorylation with PP-2A reduced the PHF wide regions by 6.0 nm and the thin regions by 2.6 nm...
  90. ncbi Bilateral injection of isoproterenol into hippocampus induces Alzheimer-like hyperphosphorylation of tau and spatial memory deficit in rat
    Li Sun
    Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, Wuhan 430030, PR China
    FEBS Lett 579:251-8. 2005
    ..These findings suggest the involvement of PKA and PKA-mediated signaling pathway in the Alzheimer-like tau hyperphosphorylation and memory impairment...
  91. ncbi Tau becomes a more favorable substrate for GSK-3 when it is prephosphorylated by PKA in rat brain
    Shi Jie Liu
    Pathophysiology Department, Neuroscience Institute, Tongji Medical College, Hua-Zhong University of Science and Technology, Wuhan 430030, People's Republic of China
    J Biol Chem 279:50078-88. 2004
    ..These data provide a novel mechanism of the hyperphosphorylation of tau and identify both PKA and GSK-3 as promising therapeutic targets for AD and other tauopathies...
  92. ncbi Up-regulation of cell division cycle (cdc) 2 kinase in neurons with early stage Alzheimer's disease neurofibrillary degeneration
    Jin Jing Pei
    Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, KFC Plan 4, Novum, 141 86 Huddinge, Sweden
    Acta Neuropathol 104:369-76. 2002
    ....
  93. ncbi What is aging? What is its role in Alzheimer's disease? What can we do about it?
    J Wesson Ashford
    Stanford VA Alzheimer Center, Palo Alto, CA 94304 1207, USA
    J Alzheimers Dis 7:247-53; discussion 255-62. 2005
  94. ncbi Folding of Alzheimer's core PHF subunit revealed by monoclonal antibody 423
    Rostislav Skrabana
    Axon Neuroscience, Rennweg 95B, 1030 Vienna, Austria
    FEBS Lett 568:178-82. 2004
    ..Since PHF represents a compelling drug target in AD, structural knowledge presented could contribute to structure-based drug design...