Fraldi, A., Klein, A.D., Medina, D.L., Settembre, C.
Brain Disorders Due to Lysosomal Dysfunction
(2016) Annual Review of Neuroscience, 39, pp. 277-295.
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84979620089&partnerID=40&md5=31b0b4e2a9538270f88c9eb948228824
DOI: 10.1146/annurev-neuro-070815-014031
AFFILIATIONS: Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy;
Dulbecco Telethon Institute, Pozzuoli, Italy;
Medical Genetics Unit, Department of Medical and Translational Science, Federico II University, Naples, Italy
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 now known to be 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. Copyright ©2016 by Annual Reviews.
