Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation

Abstract The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we...

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Autores principales:	Paula Ramos-Gonzalez, Susana Mato, Juan Carlos Chara, Alexei Verkhratsky, Carlos Matute, Fabio Cavaliere
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/6caf315b9ef544218a6118c4473e1b8b
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spelling	oai:doaj.org-article:6caf315b9ef544218a6118c4473e1b8b2021-12-02T18:17:56ZAstrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation10.1038/s41531-021-00175-w2373-8057https://doaj.org/article/6caf315b9ef544218a6118c4473e1b8b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00175-whttps://doaj.org/toc/2373-8057Abstract The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived astrocytes from PD patients with LRRK2(G2019S) mutation and healthy donors of the similar age. In cell lines derived from PD patients, astrocytes were characterised by a significant decrease in S100B and GFAP-positive astrocytic profiles associated with marked decrease in astrocyte complexity. In addition, PD-derived astrocytes demonstrated aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species. Taken together, our data indicate that astrocytic asthenia observed in patient-derived cultures with LRRK2(G2019S) mutation may contribute to neuronal death through decreased homoeostatic support, elevated oxidative stress and failed neuroprotection.Paula Ramos-GonzalezSusana MatoJuan Carlos CharaAlexei VerkhratskyCarlos MatuteFabio CavaliereNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Paula Ramos-Gonzalez Susana Mato Juan Carlos Chara Alexei Verkhratsky Carlos Matute Fabio Cavaliere Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
description	Abstract The principal hallmark of Parkinson’s disease (PD) is the selective neurodegeneration of dopaminergic neurones. Mounting evidence suggests that astrocytes may contribute to dopaminergic neurodegeneration through decreased homoeostatic support and deficient neuroprotection. In this study, we generated induced pluripotent stem cells (iPSC)-derived astrocytes from PD patients with LRRK2(G2019S) mutation and healthy donors of the similar age. In cell lines derived from PD patients, astrocytes were characterised by a significant decrease in S100B and GFAP-positive astrocytic profiles associated with marked decrease in astrocyte complexity. In addition, PD-derived astrocytes demonstrated aberrant mitochondrial morphology, decreased mitochondrial activity and ATP production along with an increase of glycolysis and increased production of reactive oxygen species. Taken together, our data indicate that astrocytic asthenia observed in patient-derived cultures with LRRK2(G2019S) mutation may contribute to neuronal death through decreased homoeostatic support, elevated oxidative stress and failed neuroprotection.
format	article
author	Paula Ramos-Gonzalez Susana Mato Juan Carlos Chara Alexei Verkhratsky Carlos Matute Fabio Cavaliere
author_facet	Paula Ramos-Gonzalez Susana Mato Juan Carlos Chara Alexei Verkhratsky Carlos Matute Fabio Cavaliere
author_sort	Paula Ramos-Gonzalez
title	Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_short	Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_full	Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_fullStr	Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_full_unstemmed	Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation
title_sort	astrocytic atrophy as a pathological feature of parkinson’s disease with lrrk2 mutation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6caf315b9ef544218a6118c4473e1b8b
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Astrocytic atrophy as a pathological feature of Parkinson’s disease with LRRK2 mutation

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