p38alpha stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis

TY - JOUR

T1 - p38alpha stress-activated protein kinase phosphorylates neurofilaments and is associated with neurofilament pathology in amyotrophic lateral sclerosis

AU - Ackerley, S

AU - Grierson, A J

AU - Banner, S

AU - Perkinton, M S

AU - Brownlees, J

AU - Byers, H L

AU - Ward, M

AU - Thornhill, P

AU - Hussain, K

AU - Waby, J S

AU - Anderton, B H

AU - Cooper, J D

AU - Dingwall, C

AU - Leigh, P N

AU - Shaw, C E

AU - Miller, C C J

PY - 2004/6

Y1 - 2004/6

N2 - 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. (C) 2004 Elsevier Inc. All rights reserved.

AB - 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. (C) 2004 Elsevier Inc. All rights reserved.

UR - http://www.scopus.com/inward/record.url?scp=4644362726&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2004.02.009

DO - 10.1016/j.mcn.2004.02.009

M3 - Article

VL - 26

SP - 354

EP - 364

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

IS - 2

ER -