The Role of Skeletal Muscle in Amyotrophic Lateral Sclerosis
Jean-Philippe Loeffler,Jean-Philippe Loeffler,Gina Picchiarelli,Gina Picchiarelli,Luc Dupuis,Luc Dupuis,Jose-Luis Gonzalez de Aguilar,Jose-Luis Gonzalez de Aguilar +7 more
TLDR
The features of ALS muscle pathology are described and the contribution of muscle to the pathological process is discussed and an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons is given.Abstract:
Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset disease primarily characterized by upper and lower motor neuron degeneration, muscle wasting and paralysis. It is increasingly accepted that the pathological process leading to ALS is the result of multiple disease mechanisms that operate within motor neurons and other cell types both inside and outside the central nervous system. The implication of skeletal muscle has been the subject of a number of studies conducted on patients and related animal models. In this review, we describe the features of ALS muscle pathology and discuss on the contribution of muscle to the pathological process. We also give an overview of the therapeutic strategies proposed to alleviate muscle pathology or to deliver curative agents to motor neurons. ALS muscle mainly suffers from oxidative stress, mitochondrial dysfunction and bioenergetic disturbances. However, the way by which the disease affects different types of myofibers depends on their contractile and metabolic features. Although the implication of muscle in nourishing the degenerative process is still debated, there is compelling evidence suggesting that it may play a critical role. Detailed understanding of the muscle pathology in ALS could, therefore, lead to the identification of new therapeutic targets.read more
Citations
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Energy metabolism in ALS: an underappreciated opportunity?
TL;DR: This work reviews metabolic alterations present in ALS patients and models, discusses the selective vulnerability of motor neurons to energetic stress, and provides an overview of tested and emerging metabolic approaches to treat ALS.
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Hypermetabolism in ALS is associated with greater functional decline and shorter survival.
Frederik J. Steyn,Zara A. Ioannides,Ruben P A van Eijk,Susan Heggie,Kathryn A Thorpe,Amelia Ceslis,Saman Heshmat,Anjali K. Henders,Naomi R. Wray,Naomi R. Wray,Leonard H. van den Berg,Robert D. Henderson,Pamela A. McCombe,Shyuan T. Ngo +13 more
TL;DR: Hypermetabolic patients with ALS have a greater level of lower motor neuron involvement, faster rate of functional decline and shorter survival, and the metabolic index could be important for informing prognosis in ALS.
Journal ArticleDOI
Molecular and Cellular Mechanisms Affected in ALS.
Laura Le Gall,Laura Le Gall,Ekene Anakor,Owen Connolly,Udaya Geetha Vijayakumar,William Duddy,Stephanie Duguez +6 more
TL;DR: A cohesive understanding of the molecular functions of ALS-associated genes may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches.
Journal ArticleDOI
MicroRNAs as Biomarkers in Amyotrophic Lateral Sclerosis.
TL;DR: The state of the art of miRNA biomarker identification for ALS in cerebrospinal fluid, blood and muscle tissue is reviewed; advantages and disadvantages of different approaches are discussed, and underline the limits but also the great potential of this research for future practical applications.
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Neuromuscular Junction Dismantling in Amyotrophic Lateral Sclerosis
TL;DR: The recent literature regarding the mechanisms leading to neuromuscular junction disassembly and muscle denervation focusing on the role of the three players of this peripheral tripartite synapse are reviewed.
References
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Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis
TL;DR: Tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O–2 to O2 and H2O2 is reported.
Journal ArticleDOI
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS
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Mark E. Gurney,Haifeng Pu,Arlene Y. Chiu,Mauro C. Dal Canto,Cynthia Y. Polchow,Denise D. Alexander,Jan Caliendo,Afif Hentati,Young W. Kwon,Han Xiang Deng,W. Chen,Ping Zhai,Robert L. Sufit,Teepu Siddique +13 more
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Journal ArticleDOI
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
Jemeen Sreedharan,Ian P. Blair,Vineeta B. Tripathi,Xun Hu,Caroline Vance,Boris Rogelj,Steven Ackerley,Steven Ackerley,Jennifer C Durnall,Kelly L. Williams,Emanuele Buratti,Francisco E. Baralle,Jacqueline de Belleroche,J. Douglas Mitchell,P. Nigel Leigh,Ammar Al-Chalabi,Christopher C.J. Miller,Christopher C.J. Miller,Garth A. Nicholson,Garth A. Nicholson,Christopher Shaw +20 more
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Journal ArticleDOI
Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis.
Thomas J. Kwiatkowski,D. A. Bosco,D. A. Bosco,A. L. LeClerc,A. L. LeClerc,Eric Tamrazian,Charles R. Vanderburg,Carsten Russ,Carsten Russ,A. Davis,James M. Gilchrist,E. J. Kasarskis,Theodore L. Munsat,Paul N. Valdmanis,Guy A. Rouleau,Betsy A. Hosler,Pietro Cortelli,P. J. De Jong,Yuko Yoshinaga,Jonathan L. Haines,Margaret A. Pericak-Vance,Jianhua Yan,Nicola Ticozzi,Nicola Ticozzi,Nicola Ticozzi,Teepu Siddique,Diane McKenna-Yasek,Peter C. Sapp,Peter C. Sapp,H R Horvitz,John Landers,John Landers,Robert H. Brown,Robert H. Brown +33 more
TL;DR: Neuronal cytoplasmic protein aggregation and defective RNA metabolism thus appear to be common pathogenic mechanisms involved in ALS and possibly in other neurodegenerative disorders.