The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau.

Abstract:

:In Pick disease and progressive supranuclear palsy (PSP), accumulations of phosphorylated tau are associated with oxidative stress, although the mechanism linking these features remains unknown. However, we suspected that the oxidative stress-induced activation of mitogen-activated protein kinases might lead to tau phosphorylation and accumulation as characteristic inclusion bodies. To test this notion, we investigated whether the activation of mitogen-activated protein kinases is involved in the pathogenesis of Pick disease and PSP. Our results show that the lesions of both Pick disease and PSP are associated with the activation of the p38 pathway (phospho-MKK6 and phospho-p38), one of the best characterized of the mitogen-activated protein kinase pathways. Based on these findings, we propose that the phosphorylation of tau is a direct consequence of the oxidative stress-induced activation of mitogen-activated protein kinases, including p38.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Hartzler AW,Zhu X,Siedlak SL,Castellani RJ,Avilá J,Perry G,Smith MA

doi

10.1016/s0197-4580(02)00029-5

subject

Has Abstract

pub_date

2002-09-01 00:00:00

pages

855-9

issue

5

eissn

0197-4580

issn

1558-1497

pii

S0197458002000295

journal_volume

23

pub_type

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