Autophagic and endo-lysosomal dysfunction in neurodegenerative disease

Malik, Bilal R., Maddison, Daniel C. ORCID: https://orcid.org/0000-0003-3038-1687, Smith, Gaynor A. ORCID: https://orcid.org/0000-0003-4332-8383 and Peters, Owen M. ORCID: https://orcid.org/0000-0002-6824-0663 2019. Autophagic and endo-lysosomal dysfunction in neurodegenerative disease. Molecular Brain 12 (1) , 100. 10.1186/s13041-019-0504-x

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Abstract

Due to their post-mitotic state, metabolic demands and often large polarised morphology, the function and survival of neurons is dependent on an efficient cellular waste clearance system both for generation of materials for metabolic processes and removal of toxic components. It is not surprising therefore that deficits in protein clearance can tip the balance between neuronal health and death. Here we discuss how autophagy and lysosome-mediated degradation pathways are disrupted in several neurological disorders. Both genetic and cell biological evidence show the diversity and complexity of vesicular clearance dysregulation in cells, and together may ultimately suggest a unified mechanism for neuronal demise in degenerative conditions. Causative and risk-associated mutations in Alzheimer’s disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson’s disease, Huntington’s disease and others have given the field a unique mechanistic insight into protein clearance processes in neurons. Through their broad implication in neurodegenerative diseases, molecules involved in these genetic pathways, in particular those involved in autophagy, are emerging as appealing therapeutic targets for intervention in neurodegeneration.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences Medicine
Publisher:	Springer
ISSN:	1756-6606
Date of First Compliant Deposit:	9 December 2019
Date of Acceptance:	1 October 2019
Last Modified:	06 Jan 2024 04:40
URI:	https://orca.cardiff.ac.uk/id/eprint/127399

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