Transient cerebral ischemia induces site-specific hyperphosphorylation of tau protein.

Abstract:

:Neurofibrillary tangles (NFTs) are a pathological hallmark of many neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP17). However, the cellular origin and the consequence of the NFT formation are poorly understood. Epidemiological evidence suggests a much higher occurrence of dementia in stroke patients. This may represent the pathogenesis of sporadic AD, which accounts for the majority of AD occurrence. Here we show that after a transient cerebral ischemia, hyperphosphorylated tau accumulates in cortical neurons in a site-specific manner. The hyperphosphorylated tau presents a conformation similar to those present in human tauopathies, and colocalizes largely with signs of apoptosis. Our current study suggests that tau hyperphosphorylation may contribute to the brain damage induced by transient cerebral ischemia, and may be involved in the pathogenesis of neurodegenerative disorders in patients after stroke. Further, these results indicate that ischemic neuronal damage and apoptosis associates with tau hyperphosphorylation, and potentially NFTs formation. Finally, our results also suggest that neuronal apoptosis may be a therapeutic target in preventing tauopathy-related neurodegenerative diseases.

journal_name

Brain Res

journal_title

Brain research

authors

Wen Y,Yang S,Liu R,Simpkins JW

doi

10.1016/j.brainres.2004.05.106

subject

Has Abstract

pub_date

2004-10-01 00:00:00

pages

30-8

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

S0006899304008583

journal_volume

1022

pub_type

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