Niemann–Pick type C disease: cellular pathology and pharmacotherapy
| Autor: | Simon Wheeler, Daniel J. Sillence |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cellular pathology Endosome GBA2 Biology Bioinformatics Biochemistry Protein Structure Secondary lipids 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Niemann-Pick C1 Protein Lysosome Autophagy medicine Animals Humans Sphingolipids Niemann-Pick Disease Type C Niemann–Pick Endolysosome Sphingolipid Endocytosis Mitochondria NPC1 endolysosome Cholesterol 030104 developmental biology medicine.anatomical_structure Gaucher Glycolipids Lysosomes Cholesterol storage 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neurochemistry. 153:674-692 |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Niemann-Pick type C disease (NPCD) was first described in 1914 and affects approximately 1 in 150,000 live births. It is characterised clinically by diverse symptoms affecting liver, spleen, motor control and brain; premature death invariably results.Its molecular originswere traced, as late as 1997, to a protein of late endosomes and lysosomes which was named NPC1. Mutation or absence of this protein leads to accumulation of cholesterol in these organelles. In this review we focus on the intracellular events that drive the pathology of this disease. We first introduce endocytosis, a much-studied area of dysfunction in NPCD cells, and survey the various ways in which this process malfunctions. We briefly consider autophagy before attempting to map the more complex pathways by which lysosomal cholesterol storage leads to protein misregulation, mitochondrial dysfunction and cell death. We then briefly introduce the metabolic pathways of sphingolipids (as these emerge as key species for treatment) and critically examine the various treatment approaches that have been attempted to date. |
| Databáze: | OpenAIRE |
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