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High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease

Alzheimer's disease (AD), the most common cause of dementia, affects millions of people worldwide. Suggested mechanisms of neurotoxicity in AD include impaired calcium (Ca(2+)) homeostasis and mitochondrial dysfunction, both contributing to neuronal damage. Little was known about the exact mito...

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Autores principales: Calvo-Rodriguez, Maria, Bacskai, Brian J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328672/
https://www.ncbi.nlm.nih.gov/pubmed/32656500
http://dx.doi.org/10.15698/cst2020.07.226
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author Calvo-Rodriguez, Maria
Bacskai, Brian J.
author_facet Calvo-Rodriguez, Maria
Bacskai, Brian J.
author_sort Calvo-Rodriguez, Maria
collection PubMed
description Alzheimer's disease (AD), the most common cause of dementia, affects millions of people worldwide. Suggested mechanisms of neurotoxicity in AD include impaired calcium (Ca(2+)) homeostasis and mitochondrial dysfunction, both contributing to neuronal damage. Little was known about the exact mitochondrial Ca(2+) homeostasis in the living brain, particularly in AD. Only now, with the development of intravital imaging techniques and transgenic mouse models of the disease, we are able to directly observe Ca(2+) levels in specific regions or particular subcellular compartments of cells, such as mitochondria. Using multiphoton microscopy, a Ca(2+) reporter targeted to mitochondria and a mouse model of cerebral β amyloidosis (APP/PS1), our recent study (Nat Comms 2020, 11:2146) found elevated mitochondrial Ca(2+) concentration in the transgenic mouse after plaque deposition, and after topical application of natural soluble amyloid beta (Aβ) oligomers to the healthy mouse brain at concentrations similar to those found in the human brain. Elevated Ca(2+) in mitochondria preceded neuronal death and could be targeted for neuroprotective therapies in AD. Here, we describe our main findings and pose new questions for future studies aimed at better understanding mitochondrial Ca(2+) dyshomeostasis in AD.
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spelling pubmed-73286722020-07-09 High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease Calvo-Rodriguez, Maria Bacskai, Brian J. Cell Stress Microreview Alzheimer's disease (AD), the most common cause of dementia, affects millions of people worldwide. Suggested mechanisms of neurotoxicity in AD include impaired calcium (Ca(2+)) homeostasis and mitochondrial dysfunction, both contributing to neuronal damage. Little was known about the exact mitochondrial Ca(2+) homeostasis in the living brain, particularly in AD. Only now, with the development of intravital imaging techniques and transgenic mouse models of the disease, we are able to directly observe Ca(2+) levels in specific regions or particular subcellular compartments of cells, such as mitochondria. Using multiphoton microscopy, a Ca(2+) reporter targeted to mitochondria and a mouse model of cerebral β amyloidosis (APP/PS1), our recent study (Nat Comms 2020, 11:2146) found elevated mitochondrial Ca(2+) concentration in the transgenic mouse after plaque deposition, and after topical application of natural soluble amyloid beta (Aβ) oligomers to the healthy mouse brain at concentrations similar to those found in the human brain. Elevated Ca(2+) in mitochondria preceded neuronal death and could be targeted for neuroprotective therapies in AD. Here, we describe our main findings and pose new questions for future studies aimed at better understanding mitochondrial Ca(2+) dyshomeostasis in AD. Shared Science Publishers OG 2020-06-18 /pmc/articles/PMC7328672/ /pubmed/32656500 http://dx.doi.org/10.15698/cst2020.07.226 Text en Copyright: © 2020 Calvo-Rodriguez and Bacskai https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Microreview
Calvo-Rodriguez, Maria
Bacskai, Brian J.
High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease
title High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease
title_full High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease
title_fullStr High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease
title_full_unstemmed High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease
title_short High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer's disease
title_sort high mitochondrial calcium levels precede neuronal death in vivo in alzheimer's disease
topic Microreview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328672/
https://www.ncbi.nlm.nih.gov/pubmed/32656500
http://dx.doi.org/10.15698/cst2020.07.226
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