Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling

Abstract Over the last 20 years, the efforts to develop new therapies for Parkinson’s disease (PD) have focused not only on the improvement of symptomatic therapy for motor and non-motor symptoms but also on the discovering of the potential causes of PD, in order to develop disease-modifying treatme...

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Autores principales:	Daniela Giovannini, Federica Andreola, Paola Spitalieri, Ewa Krystyna Krasnowska, Arianna Colini Baldeschi, Simona Rossi, Federica Sangiuolo, Mauro Cozzolino, Annalucia Serafino
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/f71a3f37f5dd420c8d31ce14c1f361e4
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spelling	oai:doaj.org-article:f71a3f37f5dd420c8d31ce14c1f361e42021-11-07T12:21:27ZNatriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling10.1038/s41420-021-00723-62058-7716https://doaj.org/article/f71a3f37f5dd420c8d31ce14c1f361e42021-11-01T00:00:00Zhttps://doi.org/10.1038/s41420-021-00723-6https://doaj.org/toc/2058-7716Abstract Over the last 20 years, the efforts to develop new therapies for Parkinson’s disease (PD) have focused not only on the improvement of symptomatic therapy for motor and non-motor symptoms but also on the discovering of the potential causes of PD, in order to develop disease-modifying treatments. The emerging role of dysregulation of the Wnt/β-catenin signaling in the onset and progression of PD, as well as of other neurodegenerative diseases (NDs), renders the targeting of this signaling an attractive therapeutic opportunity for curing this brain disorder. The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are cardiac and vascular-derived hormones also widely expressed in mammalian CNS, where they seem to participate in numerous brain functions including neural development/differentiation and neuroprotection. We recently demonstrated that ANP affects the Wnt/β-catenin pathway possibly through a Frizzled receptor-mediated mechanism and that it acts as a neuroprotective agent in in vitro models of PD by upregulating this signaling. Here we provide further evidence supporting the therapeutic potential of this class of natriuretic hormones. Specifically, we demonstrate that all the three natriuretic peptides are neuroprotective for SHSY5Y cells and primary cultures of DA neurons from mouse brain, subjected to neurotoxin insult with 6-hydroxydopamine (6-OHDA) for mimicking the neurodegeneration of PD, and these effects are associated with the activation of the Wnt/β-catenin pathway. Moreover, ANP, BNP, CNP are able to improve and accelerate the dopaminergic differentiation and maturation of hiPSCs-derived neural population obtained from two differed healthy donors, concomitantly affecting the canonical Wnt signaling. Our results support the relevance of exogenous ANP, BNP, and CNP as attractive molecules for both neuroprotection and neurorepair in PD, and more in general, in NDs for which aberrant Wnt signaling seems to be the leading pathogenetic mechanism.Daniela GiovanniniFederica AndreolaPaola SpitalieriEwa Krystyna KrasnowskaArianna Colini BaldeschiSimona RossiFederica SangiuoloMauro CozzolinoAnnalucia SerafinoNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCell Death Discovery, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cytology QH573-671 Daniela Giovannini Federica Andreola Paola Spitalieri Ewa Krystyna Krasnowska Arianna Colini Baldeschi Simona Rossi Federica Sangiuolo Mauro Cozzolino Annalucia Serafino Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling
description	Abstract Over the last 20 years, the efforts to develop new therapies for Parkinson’s disease (PD) have focused not only on the improvement of symptomatic therapy for motor and non-motor symptoms but also on the discovering of the potential causes of PD, in order to develop disease-modifying treatments. The emerging role of dysregulation of the Wnt/β-catenin signaling in the onset and progression of PD, as well as of other neurodegenerative diseases (NDs), renders the targeting of this signaling an attractive therapeutic opportunity for curing this brain disorder. The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are cardiac and vascular-derived hormones also widely expressed in mammalian CNS, where they seem to participate in numerous brain functions including neural development/differentiation and neuroprotection. We recently demonstrated that ANP affects the Wnt/β-catenin pathway possibly through a Frizzled receptor-mediated mechanism and that it acts as a neuroprotective agent in in vitro models of PD by upregulating this signaling. Here we provide further evidence supporting the therapeutic potential of this class of natriuretic hormones. Specifically, we demonstrate that all the three natriuretic peptides are neuroprotective for SHSY5Y cells and primary cultures of DA neurons from mouse brain, subjected to neurotoxin insult with 6-hydroxydopamine (6-OHDA) for mimicking the neurodegeneration of PD, and these effects are associated with the activation of the Wnt/β-catenin pathway. Moreover, ANP, BNP, CNP are able to improve and accelerate the dopaminergic differentiation and maturation of hiPSCs-derived neural population obtained from two differed healthy donors, concomitantly affecting the canonical Wnt signaling. Our results support the relevance of exogenous ANP, BNP, and CNP as attractive molecules for both neuroprotection and neurorepair in PD, and more in general, in NDs for which aberrant Wnt signaling seems to be the leading pathogenetic mechanism.
format	article
author	Daniela Giovannini Federica Andreola Paola Spitalieri Ewa Krystyna Krasnowska Arianna Colini Baldeschi Simona Rossi Federica Sangiuolo Mauro Cozzolino Annalucia Serafino
author_facet	Daniela Giovannini Federica Andreola Paola Spitalieri Ewa Krystyna Krasnowska Arianna Colini Baldeschi Simona Rossi Federica Sangiuolo Mauro Cozzolino Annalucia Serafino
author_sort	Daniela Giovannini
title	Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling
title_short	Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling
title_full	Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling
title_fullStr	Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling
title_full_unstemmed	Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling
title_sort	natriuretic peptides are neuroprotective on in vitro models of pd and promote dopaminergic differentiation of hipscs-derived neurons via the wnt/β-catenin signaling
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/f71a3f37f5dd420c8d31ce14c1f361e4
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Natriuretic peptides are neuroprotective on in vitro models of PD and promote dopaminergic differentiation of hiPSCs-derived neurons via the Wnt/β-catenin signaling

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