RGD Reference Report - The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau. - Rat Genome Database

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

Authors: Hartzler, AW  Zhu, X  Siedlak, SL  Castellani, RJ  Avila, J  Perry, G  Smith, MA 
Citation: Hartzler AW, etal., Neurobiol Aging. 2002 Sep-Oct;23(5):855-9.
RGD ID: 7495833
Pubmed: PMID:12392790   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Map2k6  (mitogen-activated protein kinase kinase 6)

Genes (Mus musculus)
Map2k6  (mitogen-activated protein kinase kinase 6)

Genes (Homo sapiens)
MAP2K6  (mitogen-activated protein kinase kinase 6)


Additional Information