TY - JOUR
T1 - Is autophagy an elective strategy to protect neurons from dysregulated cholesterol metabolism?
AU - Piscianz, Elisa
AU - Brumatti, Liza Vecchi
AU - Tommasini, Alberto
AU - Marcuzzi, Annalisa
PY - 2019/4
Y1 - 2019/4
N2 - 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 compartments. 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.
AB - 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 compartments. 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.
KW - apoptosis
KW - autophagy
KW - cholesterol
KW - inflammation
KW - inherited disease
KW - necroptosis
KW - neuronal dysfunction
KW - neurons
UR - http://www.scopus.com/inward/record.url?scp=85059973938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059973938&partnerID=8YFLogxK
U2 - 10.4103/1673-5374.247441
DO - 10.4103/1673-5374.247441
M3 - Review article
AN - SCOPUS:85059973938
VL - 14
SP - 582
EP - 587
JO - Neural Regeneration Research
JF - Neural Regeneration Research
SN - 1673-5374
IS - 4
ER -