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Autophagic and endo-lysosomal dysfunction in neurodegenerative disease.
Malik, Bilal R; Maddison, Daniel C; Smith, Gaynor A; Peters, Owen M.
Afiliação
  • Malik BR; UK Dementia Research Institute at Cardiff University, Cardiff, Wales, UK.
  • Maddison DC; School of Biosciences, Cardiff University, Cardiff, Wales, UK.
  • Smith GA; UK Dementia Research Institute at Cardiff University, Cardiff, Wales, UK.
  • Peters OM; School of Medicine, Cardiff University, Cardiff, Wales, UK.
Mol Brain ; 12(1): 100, 2019 11 29.
Article em En | MEDLINE | ID: mdl-31783880
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Doenças Neurodegenerativas / Lisossomos Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Doenças Neurodegenerativas / Lisossomos Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article