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Amyotrophic Lateral Sclerosis and Autophagy: Dysfunction and Therapeutic Targeting

Cells (Basel, Switzerland), 2020-11, Vol.9 (11), p.2413 [Peer Reviewed Journal]

COPYRIGHT 2020 MDPI AG ;2020 by the authors. 2020 ;ISSN: 2073-4409 ;EISSN: 2073-4409 ;DOI: 10.3390/cells9112413 ;PMID: 33158177

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  • Title:
    Amyotrophic Lateral Sclerosis and Autophagy: Dysfunction and Therapeutic Targeting
  • Author: Amin, Azin ; Perera, Nirma D ; Beart, Philip M ; Turner, Bradley J ; Shabanpoor, Fazel
  • Subjects: Amyotrophic lateral sclerosis ; autophagy ; Autophagy (Cytology) ; Care and treatment ; Development and progression ; Health aspects ; motor neuron disease ; Review ; therapeutics
  • Is Part Of: Cells (Basel, Switzerland), 2020-11, Vol.9 (11), p.2413
  • Description: Over the past 20 years, there has been a drastically increased understanding of the genetic basis of Amyotrophic Lateral Sclerosis. Despite the identification of more than 40 different ALS-causing mutations, the accumulation of neurotoxic misfolded proteins, inclusions, and aggregates within motor neurons is the main pathological hallmark in all cases of ALS. These protein aggregates are proposed to disrupt cellular processes and ultimately result in neurodegeneration. One of the main reasons implicated in the accumulation of protein aggregates may be defective autophagy, a highly conserved intracellular "clearance" system delivering misfolded proteins, aggregates, and damaged organelles to lysosomes for degradation. Autophagy is one of the primary stress response mechanisms activated in highly sensitive and specialised neurons following insult to ensure their survival. The upregulation of autophagy through pharmacological autophagy-inducing agents has largely been shown to reduce intracellular protein aggregate levels and disease phenotypes in different in vitro and in vivo models of neurodegenerative diseases. In this review, we explore the intriguing interface between ALS and autophagy, provide a most comprehensive summary of autophagy-targeted drugs that have been examined or are being developed as potential treatments for ALS to date, and discuss potential therapeutic strategies for targeting autophagy in ALS.
  • Publisher: Switzerland: MDPI AG
  • Language: English
  • Identifier: ISSN: 2073-4409
    EISSN: 2073-4409
    DOI: 10.3390/cells9112413
    PMID: 33158177
  • Source: PubMed Central
    ROAD: Directory of Open Access Scholarly Resources
    ProQuest Central
    DOAJ Directory of Open Access Journals
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