Metabolic alterations in Parkinson’s disease astrocytes

Abstract In Parkinson`s disease (PD), the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta is associated with Lewy bodies arising from the accumulation of alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a disease of the DA ne...

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Autores principales:	Tuuli-Maria Sonninen, Riikka H. Hämäläinen, Marja Koskuvi, Minna Oksanen, Anastasia Shakirzyanova, Sara Wojciechowski, Katja Puttonen, Nikolay Naumenko, Gundars Goldsteins, Nihay Laham-Karam, Marko Lehtonen, Pasi Tavi, Jari Koistinaho, Šárka Lehtonen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fcb1196617224db18b53e46c1fc7df9b
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spelling	oai:doaj.org-article:fcb1196617224db18b53e46c1fc7df9b2021-12-02T19:09:30ZMetabolic alterations in Parkinson’s disease astrocytes10.1038/s41598-020-71329-82045-2322https://doaj.org/article/fcb1196617224db18b53e46c1fc7df9b2020-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-71329-8https://doaj.org/toc/2045-2322Abstract In Parkinson`s disease (PD), the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta is associated with Lewy bodies arising from the accumulation of alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a disease of the DA neurons, a glial contribution, in particular that of astrocytes, in PD pathogenesis is starting to be uncovered. Here, we report findings from astrocytes derived from induced pluripotent stem cells of LRRK2 G2019S mutant patients, with one patient also carrying a GBA N370S mutation, as well as healthy individuals. The PD patient astrocytes manifest the hallmarks of the disease pathology including increased expression of alpha-synuclein. This has detrimental consequences, resulting in altered metabolism, disturbed Ca2+ homeostasis and increased release of cytokines upon inflammatory stimulation. Furthermore, PD astroglial cells manifest increased levels of polyamines and polyamine precursors while lysophosphatidylethanolamine levels are decreased, both of these changes have been reported also in PD brain. Collectively, these data reveal an important role for astrocytes in PD pathology and highlight the potential of iPSC-derived cells in disease modeling and drug discovery.Tuuli-Maria SonninenRiikka H. HämäläinenMarja KoskuviMinna OksanenAnastasia ShakirzyanovaSara WojciechowskiKatja PuttonenNikolay NaumenkoGundars GoldsteinsNihay Laham-KaramMarko LehtonenPasi TaviJari KoistinahoŠárka LehtonenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tuuli-Maria Sonninen Riikka H. Hämäläinen Marja Koskuvi Minna Oksanen Anastasia Shakirzyanova Sara Wojciechowski Katja Puttonen Nikolay Naumenko Gundars Goldsteins Nihay Laham-Karam Marko Lehtonen Pasi Tavi Jari Koistinaho Šárka Lehtonen Metabolic alterations in Parkinson’s disease astrocytes
description	Abstract In Parkinson`s disease (PD), the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta is associated with Lewy bodies arising from the accumulation of alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a disease of the DA neurons, a glial contribution, in particular that of astrocytes, in PD pathogenesis is starting to be uncovered. Here, we report findings from astrocytes derived from induced pluripotent stem cells of LRRK2 G2019S mutant patients, with one patient also carrying a GBA N370S mutation, as well as healthy individuals. The PD patient astrocytes manifest the hallmarks of the disease pathology including increased expression of alpha-synuclein. This has detrimental consequences, resulting in altered metabolism, disturbed Ca2+ homeostasis and increased release of cytokines upon inflammatory stimulation. Furthermore, PD astroglial cells manifest increased levels of polyamines and polyamine precursors while lysophosphatidylethanolamine levels are decreased, both of these changes have been reported also in PD brain. Collectively, these data reveal an important role for astrocytes in PD pathology and highlight the potential of iPSC-derived cells in disease modeling and drug discovery.
format	article
author	Tuuli-Maria Sonninen Riikka H. Hämäläinen Marja Koskuvi Minna Oksanen Anastasia Shakirzyanova Sara Wojciechowski Katja Puttonen Nikolay Naumenko Gundars Goldsteins Nihay Laham-Karam Marko Lehtonen Pasi Tavi Jari Koistinaho Šárka Lehtonen
author_facet	Tuuli-Maria Sonninen Riikka H. Hämäläinen Marja Koskuvi Minna Oksanen Anastasia Shakirzyanova Sara Wojciechowski Katja Puttonen Nikolay Naumenko Gundars Goldsteins Nihay Laham-Karam Marko Lehtonen Pasi Tavi Jari Koistinaho Šárka Lehtonen
author_sort	Tuuli-Maria Sonninen
title	Metabolic alterations in Parkinson’s disease astrocytes
title_short	Metabolic alterations in Parkinson’s disease astrocytes
title_full	Metabolic alterations in Parkinson’s disease astrocytes
title_fullStr	Metabolic alterations in Parkinson’s disease astrocytes
title_full_unstemmed	Metabolic alterations in Parkinson’s disease astrocytes
title_sort	metabolic alterations in parkinson’s disease astrocytes
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/fcb1196617224db18b53e46c1fc7df9b
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Metabolic alterations in Parkinson’s disease astrocytes

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