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Defective ATM‐p53–mediated apoptotic pathway in multiple sclerosis
Author(s) -
Deng Xinqing,
LjunggrenRose Asa,
Maas Kevin,
Sriram Subramaniam
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20600
Subject(s) - multiple sclerosis , apoptosis , neuroscience , cancer research , medicine , biology , genetics , immunology
Defective elimination of autoreactive cells is thought to play a role in the development of autoimmune diseases including multiple sclerosis (MS). We examined the activation of the ATM‐CHK2‐p53 pathway in MS patients after subjecting their peripheral blood mononuclear cells to γ‐irradiation. We found that peripheral blood mononuclear cells from a subset of MS patients show resistance to cell death induced by irradiation. This defect is due to impaired constitutive expression and activation of ATM (ataxia telangiectasia mutated), resulting in impaired stabilization of p53. We predict that these fundamental defects likely alter the regulation of the immune population of cells in MS and may contribute to the development or progression of the disease. Ann Neurol 2005;58:577–584