Amyotrophic Lateral Sclerosis (ALS) is the most common form of adult-onset motor neuron disease. It is now considered a multi-factorial and multi-systemic disorder in which alterations of the crosstalk between neuronal and non-neuronal cell types might influence the course of the disease. In this review, we will provide evidence that dysfunctions of affected muscle cells are not only a marginal consequence of denervation associated to motor neuron loss, but a direct consequence of cell muscle toxicity of mutant SOD1. In muscle, the misfolded state of mutant SOD1 protein, unlike in motor neurons, does not appear to have direct effects on protein aggregation and mitochondrial functionality. Muscle cells are, in fact, more capable than motor neurons to handle misfolded proteins, suggesting that mutant SOD1 toxicity in muscle is not mediated by classical mechanisms of intracellular misfolded protein accumulation. Several recent works indicate that a higher activation of molecular chaperones and degradative systems is present in muscle cells, which for this reason are possibly able to better manage misfolded mutant SOD1. However, several alterations in gene expression and regenerative potential of skeletal muscles have also been reported as a consequence of the expression of mutant SOD1 in muscle. Whether these changes in muscle cells are causative of ALS or a consequence of motor neuron alterations is not already clear, but their elucidation is very important, since the understanding of the mechanisms involved in mutant SOD1 toxicity in muscle may facilitate the design of treatments directed toward this specific tissue to treat ALS or at least to delay disease progression.
ALS-related misfolded protein management in motor neurons and muscle cells / M. Galbiati, V. Crippa, P. Rusmini, R. Cristofani, M.E. Cicardi, E. Giorgetti, E. Onesto, E. Messi, A. Poletti. - In: NEUROCHEMISTRY INTERNATIONAL. - ISSN 0197-0186. - 79(2014 Dec), pp. 70-78.
|Titolo:||ALS-related misfolded protein management in motor neurons and muscle cells|
|Parole Chiave:||ALS; Autophagy; Motor neurons; Muscle cells; Protein quality system|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
Settore BIO/09 - Fisiologia
|Data di pubblicazione:||dic-2014|
|Centro di ricerca:||Centro Interdipartimentale di Eccellenza per le Malattie Neurodegenerative CEND|
Centro Interuniversitario di Ricerca sulle Basi Molecolari delle Malattie Neurodegenerative
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.neuint.2014.10.007|
|Appare nelle tipologie:||01 - Articolo su periodico|