Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism?
Elisa Piscianz
Liza Vecchi Brumatti
Alberto Tommasini
Annalisa Marcuzzi
摘要：The balance of autophagy, apoptosis and necroptosis is crucial to determine the outcome of the cellular response to cholesterol dysregulation. Cholesterol plays a major role in regulating the properties of cell membranes, especially as regards their fluidity, and the regulation of its biosynthesis influences the shape and functions of these membranes. Whilst dietary cholesterol can easily be distributed to most organs, the central nervous system, whose membranes are particularly rich in cholesterol, mainly relies on de novo synthesis. For this reason, defects in the biosynthesis of cholesterol can variably affect the development of central nervous system. Moreover, defective synthesis of cholesterol and its intermediates may reflect both on structural cell anomalies and on the response to inflammatory stimuli. Examples of such disorders include mevalonate kinase deficiency, and Smith-Lemli-Opitz syndrome, due to deficiency in biosynthetic enzymes, and type C Niemann-Pick syndrome, due to altered cholesterol trafficking across cell compart-ments. Autophagy, as a crucial pathway dedicated to the degradation of cytosolic proteins and organelles, plays an essential role in the maintenance of homeostasis and in the turnover of the cytoplasmic material especially in the presence of imbalances such as those resulting from alteration of cholesterol metabolism. Manipulating the process of autophagy can offer possible strategies for improving neuronal cell viability and function in these genetic disorders.
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资助基金：This study was supported by a grant from the Institute for Maternal and Child Health–Istituto di Ricovero e Cura a Carattere Scientifico"Burlo Garofolo"–Trieste, Italy (RC 24/2017)This study was supported by a grant from the Institute for Maternal and Child Health–Istituto di Ricovero e Cura a Carattere Scientifico"Burlo Garofolo"–Trieste, Italy ( to AT)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：6( 582-587 )
英文信息