The Endolysosomal System and Proteostasis: From Development to Degeneration

• Type of Material: Article
• Authors: Bettina Winckler, University of Virginia Health System; Victor Faundez, Emory University; Sandra Maday, University of Pennsylvania; Qian Cai, Rutgers State University; Claudia Guimas Almeida, Universidade Nova de Lisboa; Huaye Zhang, Rutgers Robert Wood Johnson Medical School
• Language: English
• Date: 2018-10-31
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.1665-18.2018
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 38
• Issue: 44
• Start Page: 9364
• End Page: 9374
• Grant/Funding Information: S.M. was supported by National Institutes of Health Grant NS082619; the McCabe Fund Fellow Award; the University of Pennsylvania Alzheimer's Disease Core Center;the Intellectual and Developmental Disabilities Research Center at the Children's Hospital of Philadelphia; and the University of Pennsylvania; and the Philadelphia Foundation.; This work was supported by National Institutes of Health Grants NS081674 and NS083378 to B.W.; AG060285 to V.F.; NS089737 and NS102780 to Q.C.; and NS089578 to H.Z.; C.G.A. was supported by Maratona da Saude Award H2020/JPND (JPCOFUND/0004/2015-NAB3); and iNOVA4Health (UID/Multi/04462/2013; Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência/PT2020).
• Keywords: AUTOPHAGY-LYSOSOMAL FUNCTION; Neurosciences & Neurology; BACE1 RETROGRADE TRANSPORT; membrane trafficking; LATE ENDOSOMAL TRANSPORT; AMYOTROPHIC-LATERAL-SCLEROSIS; lysosome; Neurosciences; ALZHEIMERS-DISEASE; neurons; Life Sciences & Biomedicine; endosomes; polarity; LONG-TERM DEPRESSION; autophagy; AMYLOID PRECURSOR PROTEIN; Science & Technology; PARKIN-MEDIATED MITOPHAGY; CHOLESTEROL SENSOR ORP1L; CENTRAL-NERVOUS-SYSTEM
• Research Categories: Biology, Neuroscience; Biology, Cell

Abstract

How do neurons adapt their endolysosomal system to address the particular challenge of membrane transport across their elaborate cellular landscape and to maintain proteostasis for the lifetime of the organism? Here we review recent findings that address this central question. We discuss the cellular and molecular mechanisms of endolysosomal trafficking and the autophagy pathway in neurons, as well as their role in neuronal development and degeneration. These studies highlight the importance of understanding the basic cell biology of endolysosomal trafficking and autophagy and their roles in the maintenance of proteostasis within the context of neurons, which will be critical for developing effective therapies for various neurodevelopmental and neurodegenerative disorders.