Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders

Evidence from multiple laboratories has accumulated to show that mosaic neuronal aneuploidy and consequent apoptosis characterizes and may underlie neuronal loss in many neurodegenerative diseases, particularly Alzheimer’s disease and frontotemporal dementia. Furthermore, several neurodevelopmental...

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Main Authors: Huntington Potter, Heidi J. Chial, Julbert Caneus, Mihret Elos, Nina Elder, Sergiy Borysov, Antoneta Granic
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2019.01092/full
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author Huntington Potter
Huntington Potter
Heidi J. Chial
Heidi J. Chial
Julbert Caneus
Mihret Elos
Mihret Elos
Nina Elder
Nina Elder
Sergiy Borysov
Antoneta Granic
Antoneta Granic
Antoneta Granic
author_facet Huntington Potter
Huntington Potter
Heidi J. Chial
Heidi J. Chial
Julbert Caneus
Mihret Elos
Mihret Elos
Nina Elder
Nina Elder
Sergiy Borysov
Antoneta Granic
Antoneta Granic
Antoneta Granic
author_sort Huntington Potter
collection DOAJ
description Evidence from multiple laboratories has accumulated to show that mosaic neuronal aneuploidy and consequent apoptosis characterizes and may underlie neuronal loss in many neurodegenerative diseases, particularly Alzheimer’s disease and frontotemporal dementia. Furthermore, several neurodevelopmental disorders, including Seckel syndrome, ataxia telangiectasia, Nijmegen breakage syndrome, Niemann–Pick type C, and Down syndrome, have been shown to also exhibit mosaic aneuploidy in neurons in the brain and in other cells throughout the body. Together, these results indicate that both neurodegenerative and neurodevelopmental disorders with apparently different pathogenic causes share a cell cycle defect that leads to mosaic aneuploidy in many cell types. When such mosaic aneuploidy arises in neurons in the brain, it promotes apoptosis and may at least partly underlie the cognitive deficits that characterize the neurological symptoms of these disorders. These findings have implications for both diagnosis and treatment/prevention.
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spelling doaj.art-ac43160b720c4e6590ac43290fca8e822022-12-22T02:05:28ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-11-011010.3389/fgene.2019.01092497717Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental DisordersHuntington Potter0Huntington Potter1Heidi J. Chial2Heidi J. Chial3Julbert Caneus4Mihret Elos5Mihret Elos6Nina Elder7Nina Elder8Sergiy Borysov9Antoneta Granic10Antoneta Granic11Antoneta Granic12Department of Neurology, Rocky Mountain Alzheimer’s Disease Center, University of Colorado, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, United StatesDepartment of Neurology, Rocky Mountain Alzheimer’s Disease Center, University of Colorado, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, United StatesNanoScience Technology Center, University of Central Florida, Orlando, FL, United StatesDepartment of Neurology, Rocky Mountain Alzheimer’s Disease Center, University of Colorado, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, United StatesDepartment of Neurology, Rocky Mountain Alzheimer’s Disease Center, University of Colorado, Aurora, CO, United StatesLinda Crnic Institute for Down Syndrome, University of Colorado, Aurora, CO, United StatesDepartment of Math and Science, Saint Leo University, Saint Leo, FL, United StatesAGE Research Group, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom Newcastle University Institute for Ageing, NIHR Newcastle Biomedical Research Centre, Newcastle upon Tyne, United KingdomNewcastle upon Tyne Hospitals, NHS Foundation Trust, Newcastle upon Tyne, United KingdomEvidence from multiple laboratories has accumulated to show that mosaic neuronal aneuploidy and consequent apoptosis characterizes and may underlie neuronal loss in many neurodegenerative diseases, particularly Alzheimer’s disease and frontotemporal dementia. Furthermore, several neurodevelopmental disorders, including Seckel syndrome, ataxia telangiectasia, Nijmegen breakage syndrome, Niemann–Pick type C, and Down syndrome, have been shown to also exhibit mosaic aneuploidy in neurons in the brain and in other cells throughout the body. Together, these results indicate that both neurodegenerative and neurodevelopmental disorders with apparently different pathogenic causes share a cell cycle defect that leads to mosaic aneuploidy in many cell types. When such mosaic aneuploidy arises in neurons in the brain, it promotes apoptosis and may at least partly underlie the cognitive deficits that characterize the neurological symptoms of these disorders. These findings have implications for both diagnosis and treatment/prevention.https://www.frontiersin.org/article/10.3389/fgene.2019.01092/fullAlzheimer’s diseaseMosaic aneuploidyFrontotemporal lobar degenerationNeuronal apoptosisHuntington’s disease (HD)
spellingShingle Huntington Potter
Huntington Potter
Heidi J. Chial
Heidi J. Chial
Julbert Caneus
Mihret Elos
Mihret Elos
Nina Elder
Nina Elder
Sergiy Borysov
Antoneta Granic
Antoneta Granic
Antoneta Granic
Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders
Frontiers in Genetics
Alzheimer’s disease
Mosaic aneuploidy
Frontotemporal lobar degeneration
Neuronal apoptosis
Huntington’s disease (HD)
title Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders
title_full Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders
title_fullStr Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders
title_full_unstemmed Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders
title_short Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders
title_sort chromosome instability and mosaic aneuploidy in neurodegenerative and neurodevelopmental disorders
topic Alzheimer’s disease
Mosaic aneuploidy
Frontotemporal lobar degeneration
Neuronal apoptosis
Huntington’s disease (HD)
url https://www.frontiersin.org/article/10.3389/fgene.2019.01092/full
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