Autophagic and endo-lysosomal dysfunction in neurodegenerative disease.

Autophagic and endo-lysosomal dysfunction in neurodegenerative disease.

Publication date: Nov 29, 2019

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.

Malik, B.R., Maddison, D.C., Smith, G.A., and Peters, O.M. Autophagic and endo-lysosomal dysfunction in neurodegenerative disease. 06804. 2019 Mol Brain (12):1.

Concepts Keywords
Alzheimer Neurological disorders
Amyotrophic Lateral Sclerosis Branches of biology
Autophagy Cellular processes
Causative Senescence
Frontotemporal Dementia Cell biology
Genetic Autophagy
Huntington Immunology
Lysosomal Programmed cell death
Lysosome Mitophagy
Mitotic Neurodegeneration
Morphology Lysosome
Neurodegeneration Degenerative disease
Neurodegenerative Disease
Neurodegenerative Diseases
Neurological Disorders


Type Source Name
disease MESH neurodegenerative disease
drug DRUGBANK Isoxaflutole
disease MESH death
pathway KEGG Autophagy
pathway KEGG Lysosome
disease MESH neurological disorders
disease MESH Frontotemporal Dementia
disease MESH Amyotrophic Lateral Sclerosis
pathway KEGG Mitophagy

Original Article

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