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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2019

Open Access 01-12-2019 | Review

Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses

Authors: Anil B. Mukherjee, Abhilash P. Appu, Tamal Sadhukhan, Sydney Casey, Avisek Mondal, Zhongjian Zhang, Maria B. Bagh

Published in: Molecular Neurodegeneration | Issue 1/2019

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Abstract

Neuronal Ceroid Lipofuscinoses (NCLs), commonly known as Batten disease, constitute a group of the most prevalent neurodegenerative lysosomal storage disorders (LSDs). Mutations in at least 13 different genes (called CLNs) cause various forms of NCLs. Clinically, the NCLs manifest early impairment of vision, progressive decline in cognitive and motor functions, seizures and a shortened lifespan. At the cellular level, all NCLs show intracellular accumulation of autofluorescent material (called ceroid) and progressive neuron loss. Despite intense studies the normal physiological functions of each of the CLN genes remain poorly understood. Consequently, the development of mechanism-based therapeutic strategies remains challenging. Endolysosomal dysfunction contributes to pathogenesis of virtually all LSDs. Studies within the past decade have drastically changed the notion that the lysosomes are merely the terminal degradative organelles. The emerging new roles of the lysosome include its central role in nutrient-dependent signal transduction regulating metabolism and cellular proliferation or quiescence. In this review, we first provide a brief overview of the endolysosomal and autophagic pathways, lysosomal acidification and endosome-lysosome and autophagosome-lysosome fusions. We emphasize the importance of these processes as their dysregulation leads to pathogenesis of many LSDs including the NCLs. We also describe what is currently known about each of the 13 CLN genes and their products and how understanding the emerging new roles of the lysosome may clarify the underlying pathogenic mechanisms of the NCLs. Finally, we discuss the current and emerging therapeutic strategies for various NCLs.
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Metadata
Title
Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses
Authors
Anil B. Mukherjee
Abhilash P. Appu
Tamal Sadhukhan
Sydney Casey
Avisek Mondal
Zhongjian Zhang
Maria B. Bagh
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2019
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-018-0300-6

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