Journal article
Lysosome and endoplasmic reticulum quality control pathways in Niemann-Pick type C disease
Brain research, Vol.1649(Pt B), pp.181-188
10/15/2016
DOI: 10.1016/j.brainres.2016.03.035
PMCID: PMC5542880
PMID: 27026653
Abstract
Lysosomal storage diseases result from inherited deficiencies of lysosomal hydrolytic activities or lipid transport. Collectively, these disorders are a common cause of morbidity in the pediatric population and are often associated with severe neurodegeneration. Among this group of diseases is Niemann-Pick type C, an autosomal recessive disorder of lipid trafficking that causes cognitive impairment, ataxia and death, most often in childhood. Here, we review the current knowledge of disease pathogenesis, with particular focus on insights gleaned from genetics and the study of model systems. Critical advances in understanding mechanisms that regulate intracellular cholesterol trafficking have emerged from this work and are highlighted. We review effects of disease-causing mutations on quality control pathways involving the lysosome and endoplasmic reticulum, and discuss how they function to clear the most common mutant protein found in Niemann-Pick type C patients, NPC1-I1061T. Finally, we summarize insights into the mechanisms that degrade misfolded transmembrane proteins in the endoplasmic reticulum and how manipulating these quality control pathways may lead to the identification of novel targets for disease modifying therapies.
This article is part of a Special Issue entitled SI:Autophagy. (C) 2016 Published by Elsevier B.V.
Details
- Title: Subtitle
- Lysosome and endoplasmic reticulum quality control pathways in Niemann-Pick type C disease
- Creators
- Mark L. Schultz - University of Michigan Medical SchoolKelsey L. Krus - University of MichiganAndrew P. Lieberman - University of Michigan
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.1649(Pt B), pp.181-188
- DOI
- 10.1016/j.brainres.2016.03.035
- PMID
- 27026653
- PMCID
- PMC5542880
- NLM abbreviation
- Brain Res
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- T32NS007222 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) T32 NS007222; R01 NS063967 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 10/15/2016
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics
- Record Identifier
- 9984366277402771
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