p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis

Steven Ackerley, Andrew J. Grierson, Steven Banner, Michael S. Perkinton, Janet Brownlees, Helen L. Byers, Malcolm Ward, Paul Thornhill, Kader Hussain, Jennifer S. Waby, Brian H. Anderton, Jonathan D. Cooper, Colin Dingwall, P. Nigel Leigh, Christopher E. Shaw, Christopher C.J. Miller

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

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 p38α, 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 p38α 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.

Original languageEnglish
Pages (from-to)354-364
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume26
Issue number2
DOIs
StatePublished - Jun 2004

Fingerprint

Dive into the research topics of 'p38α stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this