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What skeletal muscle has to say in amyotrophic lateral sclerosis: Implications for therapy
Author(s) -
Manzano Raquel,
Toivonen Janne Markus,
MorenoMartínez Laura,
Torre Miriam,
MorenoGarcía Leticia,
LópezRoyo Tresa,
Moliora,
Zaragoza Pilar,
Calvo Ana Cristina,
Osta Rosario
Publication year - 2021
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15276
Subject(s) - amyotrophic lateral sclerosis , skeletal muscle , biology , neuroscience , regeneration (biology) , spinal muscular atrophy , proteostasis , neuromuscular junction , disease , neuromuscular disease , sarcopenia , pathology , medicine , anatomy , genetics
Amyotrophic lateral sclerosis (ALS) is an adult onset disorder characterized by progressive neuromuscular junction (NMJ) dismantling and degeneration of motor neurons leading to atrophy and paralysis of voluntary muscles responsible for motion and breathing. Except for a minority of patients harbouring genetic mutations, the origin of most ALS cases remains elusive. Peripheral tissues, and particularly skeletal muscle, have lately demonstrated an active contribution to disease pathology attracting a growing interest for these tissues as therapeutic targets in ALS. In this sense, molecular mechanisms essential for cell and tissue homeostasis have been shown to be deregulated in the disease. These include muscle metabolism and mitochondrial activity, RNA processing, tissue-resident stem cell function responsible for muscle regeneration, and proteostasis that regulates muscle mass in adulthood. This review aims to compile scientific evidence that demonstrates the role of skeletal muscle in ALS pathology and serves as reference for development of novel therapeutic strategies targeting this tissue to delay disease onset and progression. LINKED ARTICLES: This article is part of a themed issue on Neurochemistry in Japan. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc.