Intracellular Cholesterol Trafficking and Impact in Neurodegeneration
Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhi...
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doaj-9543bd300a4f4d41a979b258fd8147742020-11-24T22:01:27ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-11-011010.3389/fnmol.2017.00382297083Intracellular Cholesterol Trafficking and Impact in NeurodegenerationFabian Arenas0Fabian Arenas1Fabian Arenas2Carmen Garcia-Ruiz3Carmen Garcia-Ruiz4Carmen Garcia-Ruiz5Carmen Garcia-Ruiz6Jose C. Fernandez-Checa7Jose C. Fernandez-Checa8Jose C. Fernandez-Checa9Jose C. Fernandez-Checa10Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, SpainLiver Unit and Hospital Clinic I Provincial, IDIBAPS, Barcelona, SpainCentro de Investigación Biomédica en Red, CIBEREHD, Barcelona, SpainDepartment of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, SpainLiver Unit and Hospital Clinic I Provincial, IDIBAPS, Barcelona, SpainCentro de Investigación Biomédica en Red, CIBEREHD, Barcelona, SpainSouthern California Research Center for ALDP and Cirrhosis, Los Angeles, CA, United StatesDepartment of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Barcelona, SpainLiver Unit and Hospital Clinic I Provincial, IDIBAPS, Barcelona, SpainCentro de Investigación Biomédica en Red, CIBEREHD, Barcelona, SpainSouthern California Research Center for ALDP and Cirrhosis, Los Angeles, CA, United StatesCholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD), however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00382/fullcholesterollysosomesmitochondriaendoplasmic reticulummitochondria associated ER membranesAlzheimer disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fabian Arenas Fabian Arenas Fabian Arenas Carmen Garcia-Ruiz Carmen Garcia-Ruiz Carmen Garcia-Ruiz Carmen Garcia-Ruiz Jose C. Fernandez-Checa Jose C. Fernandez-Checa Jose C. Fernandez-Checa Jose C. Fernandez-Checa |
spellingShingle |
Fabian Arenas Fabian Arenas Fabian Arenas Carmen Garcia-Ruiz Carmen Garcia-Ruiz Carmen Garcia-Ruiz Carmen Garcia-Ruiz Jose C. Fernandez-Checa Jose C. Fernandez-Checa Jose C. Fernandez-Checa Jose C. Fernandez-Checa Intracellular Cholesterol Trafficking and Impact in Neurodegeneration Frontiers in Molecular Neuroscience cholesterol lysosomes mitochondria endoplasmic reticulum mitochondria associated ER membranes Alzheimer disease |
author_facet |
Fabian Arenas Fabian Arenas Fabian Arenas Carmen Garcia-Ruiz Carmen Garcia-Ruiz Carmen Garcia-Ruiz Carmen Garcia-Ruiz Jose C. Fernandez-Checa Jose C. Fernandez-Checa Jose C. Fernandez-Checa Jose C. Fernandez-Checa |
author_sort |
Fabian Arenas |
title |
Intracellular Cholesterol Trafficking and Impact in Neurodegeneration |
title_short |
Intracellular Cholesterol Trafficking and Impact in Neurodegeneration |
title_full |
Intracellular Cholesterol Trafficking and Impact in Neurodegeneration |
title_fullStr |
Intracellular Cholesterol Trafficking and Impact in Neurodegeneration |
title_full_unstemmed |
Intracellular Cholesterol Trafficking and Impact in Neurodegeneration |
title_sort |
intracellular cholesterol trafficking and impact in neurodegeneration |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2017-11-01 |
description |
Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD), however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities. |
topic |
cholesterol lysosomes mitochondria endoplasmic reticulum mitochondria associated ER membranes Alzheimer disease |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00382/full |
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