Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

In recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer’s disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key...

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Main Authors: Erica Staurenghi, Serena Giannelli, Gabriella Testa, Barbara Sottero, Gabriella Leonarduzzi, Paola Gamba
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/12/1890
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author Erica Staurenghi
Serena Giannelli
Gabriella Testa
Barbara Sottero
Gabriella Leonarduzzi
Paola Gamba
author_facet Erica Staurenghi
Serena Giannelli
Gabriella Testa
Barbara Sottero
Gabriella Leonarduzzi
Paola Gamba
author_sort Erica Staurenghi
collection DOAJ
description In recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer’s disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key role of cholesterol oxidation products, named oxysterols, has emerged. Brain cholesterol metabolism is independent from that of peripheral tissues and it must be preserved in order to guarantee cerebral functions. Among the cells that help maintain brain cholesterol homeostasis, astrocytes play a starring role since they deliver de novo synthesized cholesterol to neurons. In addition, other physiological roles of astrocytes are to modulate synaptic transmission and plasticity and support neurons providing energy. In the AD brain, astrocytes undergo significant morphological and functional changes that contribute to AD onset and development. However, the extent of this contribution and the role played by oxysterols are still unclear. Here we review the current understanding of the physiological role exerted by astrocytes in the brain and their contribution to AD pathogenesis. In particular, we focus on the impact of cholesterol dysmetabolism on astrocyte functions suggesting new potential approaches to develop therapeutic strategies aimed at counteracting AD development.
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spelling doaj.art-68f0c1d2a38f42c8b6136a92f5d0922d2023-11-23T03:32:38ZengMDPI AGAntioxidants2076-39212021-11-011012189010.3390/antiox10121890Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?Erica Staurenghi0Serena Giannelli1Gabriella Testa2Barbara Sottero3Gabriella Leonarduzzi4Paola Gamba5Department of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, ItalyDepartment of Clinical and Biological Sciences, University of Turin, Orbassano, 10043 Turin, ItalyIn recent decades, the impairment of cholesterol metabolism in the pathogenesis of Alzheimer’s disease (AD) has been intensively investigated, and it has been recognized to affect amyloid β (Aβ) production and clearance, tau phosphorylation, neuroinflammation and degeneration. In particular, the key role of cholesterol oxidation products, named oxysterols, has emerged. Brain cholesterol metabolism is independent from that of peripheral tissues and it must be preserved in order to guarantee cerebral functions. Among the cells that help maintain brain cholesterol homeostasis, astrocytes play a starring role since they deliver de novo synthesized cholesterol to neurons. In addition, other physiological roles of astrocytes are to modulate synaptic transmission and plasticity and support neurons providing energy. In the AD brain, astrocytes undergo significant morphological and functional changes that contribute to AD onset and development. However, the extent of this contribution and the role played by oxysterols are still unclear. Here we review the current understanding of the physiological role exerted by astrocytes in the brain and their contribution to AD pathogenesis. In particular, we focus on the impact of cholesterol dysmetabolism on astrocyte functions suggesting new potential approaches to develop therapeutic strategies aimed at counteracting AD development.https://www.mdpi.com/2076-3921/10/12/1890Alzheimer’s diseaseastrocytesastrocyte reactivitycholesteroloxysterolsneuroinflammation
spellingShingle Erica Staurenghi
Serena Giannelli
Gabriella Testa
Barbara Sottero
Gabriella Leonarduzzi
Paola Gamba
Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
Antioxidants
Alzheimer’s disease
astrocytes
astrocyte reactivity
cholesterol
oxysterols
neuroinflammation
title Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
title_full Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
title_fullStr Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
title_full_unstemmed Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
title_short Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?
title_sort cholesterol dysmetabolism in alzheimer s disease a starring role for astrocytes
topic Alzheimer’s disease
astrocytes
astrocyte reactivity
cholesterol
oxysterols
neuroinflammation
url https://www.mdpi.com/2076-3921/10/12/1890
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AT barbarasottero cholesteroldysmetabolisminalzheimersdiseaseastarringroleforastrocytes
AT gabriellaleonarduzzi cholesteroldysmetabolisminalzheimersdiseaseastarringroleforastrocytes
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