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Amyotrophic lateral sclerosis: all roads lead to Rome
Author(s) -
Aguilar JoseLuis Gonzalez de,
EchanizLaguna Andoni,
Fergani Anissa,
René Frédérique,
Meininger Vincent,
Loeffler JeanPhilippe,
Dupuis Luc
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04408.x
Subject(s) - amyotrophic lateral sclerosis , sod1 , neuroscience , motor neuron , disease , biology , neuron , axoplasmic transport , degenerative disease , upper motor neuron , degeneration (medical) , atrophy , medicine , pathology , central nervous system disease , genetics , spinal cord
Amyotrophic lateral sclerosis (ALS) is the most frequent adult‐onset motor neuron disease characterized by degeneration of upper and lower motor neurons, generalized weakness and muscle atrophy. Most cases of ALS appear sporadically but some forms of the disease result from mutations in the gene encoding the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). Several other mutated genes have also been found to predispose to ALS including, among others, one that encodes the regulator of axonal retrograde transport dynactin. As all roads lead to the proverbial Rome, we discuss here how distinct molecular pathways may converge to the same final result that is motor neuron death. We critically review the basic research on SOD1‐linked ALS to propose a pioneering model of a ‘systemic’ form of the disease, causally involving multiple cell types, either neuronal or non‐neuronal. Contrasting this, we also postulate that other neuron‐specific defects, as those triggered by dynactin dysfunction, may account for a primary motor neuron disease that would represent ‘pure’ neuronal forms of ALS. Identifying different disease subtypes is an unavoidable step toward the understanding of the physiopathology of ALS and will hopefully help to design specific treatments for each subset of patients.