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p38 alpha stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis

Lookup NU author(s): Professor Colin Dingwall

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Abstract

Neurofilament middle and heavy chains (NFM and NFH) are heavily phosphorylated on their carboxy-terminal side-arm domains in axons. The mechanisms that regulate this phosphorylation are complex. Here, we demonstrate that p38alpha, a member of the stress-activated protein kinase family, will phosphorylate NFM and NFH on their side-arm domains. Aberrant accumulations of neurofilaments containing phosphorylated NFM and NFH side-arms are a pathological feature of amyotrophic lateral sclerosis (ALS) and we also demonstrate that p38alpha and active forms of p38 family kinases are associated with these accumulations. This is the case for sporadic and familial forms of ALS and also in a transgenic mouse model of ALS caused by expression of mutant superoxide dismutase-1 (SOD1). Thus, p38 kinases may contribute to the aberrant phosphorylation of NFM and NFH side-arms in ALS.

Publication metadata

Author(s): Dingwall C; Ackerley S; Grierson AJ; Banner S; Perkinton MS; Brownlees J; Byers HL; Ward M; Thornhill P; Hussain K; Waby JS; Anderton BH; Cooper JD; Leigh PN; Shaw CE; Miller CCJ

Publication type: Article

Publication status: Published

Journal: Molecular and Cellular Neuroscience

Year: 2004

Volume: 26

Issue: 2

Pages: 354-364

ISSN (print): 1044-7431

ISSN (electronic): 1095-9327

Publisher: Academic Press

URL: http://dx.doi.org/10.1016/j.mcn.2004.02.009

DOI: 10.1016/j.mcn.2004.02.009

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