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Stress kinases involved in tau phosphorylation in Alzheimer's disease, tauopathies and APP transgenic mice.
Neurotox Res 2004; 6(6):469-75NR

Abstract

Hyperphosphorylation and accumulation of tau in neurons (and glial cells) is one of the main pathologic hallmarks in Alzheimer's disease (AD) and other tauopathies, including Pick's disease (PiD), progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease and familial frontotemporal dementia and parkinsonism linked to chromosome 17 due to mutations in the tau gene (FTDP-17-tau). Recent studies have shown increased expression of select active kinases, including stress-activated kinase, c-Jun N-terminal kinase (SAPK/JNK) and kinase p38 in brain homogenates in all the tauopathies. Strong active SAPK/JNK and p38 immunoreactivity has been observed restricted to neurons and glial cells containing hyperphosphorylated tau, as well as in dystrophic neurites of senile plaques in AD. Moreover, SAPK/JNK- and p38-immunoprecipitated sub-cellular fractions enriched in abnormal hyperphosphorylated tau have the capacity to phosphorylate recombinat tau and c-Jun and ATF-2 which are specific substrates of SAPK/JNK and p38 in AD and PiD. Interestingly, increased expression of phosphorylated SAPK/JNK and p38 in association with hyperphosphorylated tau containing neurites have been observed around betaA4 amyloid deposits in the brain of transgenic mice (Tg2576)carrying the double APP Swedish mutation. These findings suggest that betaA4 amyloid has the capacity to trigger the activation of stress kinases which, in turn, phosphorylate tau in neurites surrounding amyloid deposits. Reduction in the amyloid burden and decreased numbers of amyloid plaques but not of neurofibrillary degeneration has been observed in the brain of two AD patients who participated in an amyloid-beta immunization trial. Activation of stress kinases SAPK/JNK and p38 were reduced together with decreased tau hyperphosphorylation of aberrant neurites in association with decreased amyloid plaques. These findings support the amyloid cascade hypothesis of tau phosphorylation mediated by stress kinases in dystrophic neurites of senile plaques but not that of neurofibrillary tangles and neuropil threads in AD.

Authors+Show Affiliations

Institut de Neuropatologia, Servei Anatomia Patològica, Hospital de Bellvitge, Universitat de Barcelona, Hospitalet de Llobregat, Spain. iferrer@csub.scs.es

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15658002

Citation

Ferrer, I. "Stress Kinases Involved in Tau Phosphorylation in Alzheimer's Disease, Tauopathies and APP Transgenic Mice." Neurotoxicity Research, vol. 6, no. 6, 2004, pp. 469-75.
Ferrer I. Stress kinases involved in tau phosphorylation in Alzheimer's disease, tauopathies and APP transgenic mice. Neurotox Res. 2004;6(6):469-75.
Ferrer, I. (2004). Stress kinases involved in tau phosphorylation in Alzheimer's disease, tauopathies and APP transgenic mice. Neurotoxicity Research, 6(6), pp. 469-75.
Ferrer I. Stress Kinases Involved in Tau Phosphorylation in Alzheimer's Disease, Tauopathies and APP Transgenic Mice. Neurotox Res. 2004;6(6):469-75. PubMed PMID: 15658002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stress kinases involved in tau phosphorylation in Alzheimer's disease, tauopathies and APP transgenic mice. A1 - Ferrer,I, PY - 2005/1/22/pubmed PY - 2005/3/2/medline PY - 2005/1/22/entrez SP - 469 EP - 75 JF - Neurotoxicity research JO - Neurotox Res VL - 6 IS - 6 N2 - Hyperphosphorylation and accumulation of tau in neurons (and glial cells) is one of the main pathologic hallmarks in Alzheimer's disease (AD) and other tauopathies, including Pick's disease (PiD), progressive supranuclear palsy, corticobasal degeneration, argyrophilic grain disease and familial frontotemporal dementia and parkinsonism linked to chromosome 17 due to mutations in the tau gene (FTDP-17-tau). Recent studies have shown increased expression of select active kinases, including stress-activated kinase, c-Jun N-terminal kinase (SAPK/JNK) and kinase p38 in brain homogenates in all the tauopathies. Strong active SAPK/JNK and p38 immunoreactivity has been observed restricted to neurons and glial cells containing hyperphosphorylated tau, as well as in dystrophic neurites of senile plaques in AD. Moreover, SAPK/JNK- and p38-immunoprecipitated sub-cellular fractions enriched in abnormal hyperphosphorylated tau have the capacity to phosphorylate recombinat tau and c-Jun and ATF-2 which are specific substrates of SAPK/JNK and p38 in AD and PiD. Interestingly, increased expression of phosphorylated SAPK/JNK and p38 in association with hyperphosphorylated tau containing neurites have been observed around betaA4 amyloid deposits in the brain of transgenic mice (Tg2576)carrying the double APP Swedish mutation. These findings suggest that betaA4 amyloid has the capacity to trigger the activation of stress kinases which, in turn, phosphorylate tau in neurites surrounding amyloid deposits. Reduction in the amyloid burden and decreased numbers of amyloid plaques but not of neurofibrillary degeneration has been observed in the brain of two AD patients who participated in an amyloid-beta immunization trial. Activation of stress kinases SAPK/JNK and p38 were reduced together with decreased tau hyperphosphorylation of aberrant neurites in association with decreased amyloid plaques. These findings support the amyloid cascade hypothesis of tau phosphorylation mediated by stress kinases in dystrophic neurites of senile plaques but not that of neurofibrillary tangles and neuropil threads in AD. SN - 1029-8428 UR - https://www.unboundmedicine.com/medline/citation/15658002/Stress_kinases_involved_in_tau_phosphorylation_in_Alzheimer's_disease_tauopathies_and_APP_transgenic_mice_ L2 - https://dx.doi.org/10.1007/bf03033283 DB - PRIME DP - Unbound Medicine ER -