ALS-related misfolded protein management in motor neurons and muscle cells

Mariarita Galbiati, Valeria Crippa, Paola Rusmini, Riccardo Cristofani, Maria E lena Cicardi, Elisa Giorgetti, Elisa Onesto, Elio Messi, Angelo Poletti

Research output: Contribution to journalArticle

Abstract

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 neurons 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 proteins 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 yet 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.

Original languageEnglish
Pages (from-to)70-78
Number of pages9
JournalNeurochemistry International
Volume79
DOIs
Publication statusPublished - Dec 1 2014

Fingerprint

Amyotrophic Lateral Sclerosis
Motor Neurons
Muscle Cells
Muscles
Mutant Proteins
Proteins
Motor Neuron Disease
Molecular Chaperones
Mitochondrial Proteins
Denervation
Disease Progression
Skeletal Muscle
Gene Expression

Keywords

  • ALS
  • Autophagy
  • Motor neurons
  • Muscle cells
  • Protein quality system

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Galbiati, M., Crippa, V., Rusmini, P., Cristofani, R., Cicardi, M. E. L., Giorgetti, E., ... Poletti, A. (2014). ALS-related misfolded protein management in motor neurons and muscle cells. Neurochemistry International, 79, 70-78. https://doi.org/10.1016/j.neuint.2014.10.007

ALS-related misfolded protein management in motor neurons and muscle cells. / Galbiati, Mariarita; Crippa, Valeria; Rusmini, Paola; Cristofani, Riccardo; Cicardi, Maria E lena; Giorgetti, Elisa; Onesto, Elisa; Messi, Elio; Poletti, Angelo.

In: Neurochemistry International, Vol. 79, 01.12.2014, p. 70-78.

Research output: Contribution to journalArticle

Galbiati, M, Crippa, V, Rusmini, P, Cristofani, R, Cicardi, MEL, Giorgetti, E, Onesto, E, Messi, E & Poletti, A 2014, 'ALS-related misfolded protein management in motor neurons and muscle cells', Neurochemistry International, vol. 79, pp. 70-78. https://doi.org/10.1016/j.neuint.2014.10.007
Galbiati M, Crippa V, Rusmini P, Cristofani R, Cicardi MEL, Giorgetti E et al. ALS-related misfolded protein management in motor neurons and muscle cells. Neurochemistry International. 2014 Dec 1;79:70-78. https://doi.org/10.1016/j.neuint.2014.10.007
Galbiati, Mariarita ; Crippa, Valeria ; Rusmini, Paola ; Cristofani, Riccardo ; Cicardi, Maria E lena ; Giorgetti, Elisa ; Onesto, Elisa ; Messi, Elio ; Poletti, Angelo. / ALS-related misfolded protein management in motor neurons and muscle cells. In: Neurochemistry International. 2014 ; Vol. 79. pp. 70-78.
@article{393231e0f09a49fd815ea61db77e0831,
title = "ALS-related misfolded protein management in motor neurons and muscle cells",
abstract = "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 neurons 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 proteins 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 yet 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.",
keywords = "ALS, Autophagy, Motor neurons, Muscle cells, Protein quality system",
author = "Mariarita Galbiati and Valeria Crippa and Paola Rusmini and Riccardo Cristofani and Cicardi, {Maria E lena} and Elisa Giorgetti and Elisa Onesto and Elio Messi and Angelo Poletti",
year = "2014",
month = "12",
day = "1",
doi = "10.1016/j.neuint.2014.10.007",
language = "English",
volume = "79",
pages = "70--78",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - ALS-related misfolded protein management in motor neurons and muscle cells

AU - Galbiati, Mariarita

AU - Crippa, Valeria

AU - Rusmini, Paola

AU - Cristofani, Riccardo

AU - Cicardi, Maria E lena

AU - Giorgetti, Elisa

AU - Onesto, Elisa

AU - Messi, Elio

AU - Poletti, Angelo

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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 neurons 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 proteins 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 yet 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.

AB - 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 neurons 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 proteins 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 yet 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.

KW - ALS

KW - Autophagy

KW - Motor neurons

KW - Muscle cells

KW - Protein quality system

UR - http://www.scopus.com/inward/record.url?scp=84938519018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84938519018&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2014.10.007

DO - 10.1016/j.neuint.2014.10.007

M3 - Article

C2 - 25451799

VL - 79

SP - 70

EP - 78

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

ER -