Recent studies of autophagic and lysosomal pathways have significantly changed our understanding of lysosomes; once thought to be simple degradative and recycling centers, lysosomes are actually organelles capable of influencing signal transduction, via the mammalian target of rapamycin complex 1 (mTORC1), and regulating gene expression, via transcription factor EB (TFEB) and other transcription factors. These pathways are particularly relevant to maintaining brain homeostasis, as dysfunction of the endolysosomal and autophagic pathways has been associated with common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, and lysosomal storage disorders, a group of inherited disorders characterized by the intralysosomal buildup of partially degraded metabolites. This review focuses on the cellular biology of lysosomes and discusses the possible mechanisms by which disruption of their function contributes to neurodegeneration. We also review and discuss how targeting TFEB and lysosomes may offer innovative therapeutic approaches for treating a wide range of neurological conditions. Expected final online publication date for the Annual Review of Neuroscience Volume 39 is July 08, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Brain Disorders Due to Lysomal Dysfunction / Fraldi, Alessandro; Klein, Andrés D; Medina, Diego Luis; Settembre, Carmine. - In: ANNUAL REVIEW OF NEUROSCIENCE. - ISSN 0147-006X. - 39:1(2016). [10.1146/annurev-neuro-070815-014031]

Brain Disorders Due to Lysomal Dysfunction

Fraldi, Alessandro;Medina, Diego Luis;
2016

Abstract

Recent studies of autophagic and lysosomal pathways have significantly changed our understanding of lysosomes; once thought to be simple degradative and recycling centers, lysosomes are actually organelles capable of influencing signal transduction, via the mammalian target of rapamycin complex 1 (mTORC1), and regulating gene expression, via transcription factor EB (TFEB) and other transcription factors. These pathways are particularly relevant to maintaining brain homeostasis, as dysfunction of the endolysosomal and autophagic pathways has been associated with common neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's, and lysosomal storage disorders, a group of inherited disorders characterized by the intralysosomal buildup of partially degraded metabolites. This review focuses on the cellular biology of lysosomes and discusses the possible mechanisms by which disruption of their function contributes to neurodegeneration. We also review and discuss how targeting TFEB and lysosomes may offer innovative therapeutic approaches for treating a wide range of neurological conditions. Expected final online publication date for the Annual Review of Neuroscience Volume 39 is July 08, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
2016
Brain Disorders Due to Lysomal Dysfunction / Fraldi, Alessandro; Klein, Andrés D; Medina, Diego Luis; Settembre, Carmine. - In: ANNUAL REVIEW OF NEUROSCIENCE. - ISSN 0147-006X. - 39:1(2016). [10.1146/annurev-neuro-070815-014031]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/634500
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