Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor

Abstract The lack of disease-modifying treatments for Parkinson’s disease (PD) is in part due to an incomplete understanding of the disease’s etiology. Alpha-synuclein (α-syn) has become a point of focus in PD due to its connection to both familial and idiopathic cases—specifically its localization...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kathryn M. Miller, Natosha M. Mercado, Caryl E. Sortwell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/f5cdec01b89e4bc586532d9150c98dee
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f5cdec01b89e4bc586532d9150c98dee
record_format	dspace
spelling	oai:doaj.org-article:f5cdec01b89e4bc586532d9150c98dee2021-12-02T14:27:57ZSynucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor10.1038/s41531-021-00179-62373-8057https://doaj.org/article/f5cdec01b89e4bc586532d9150c98dee2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00179-6https://doaj.org/toc/2373-8057Abstract The lack of disease-modifying treatments for Parkinson’s disease (PD) is in part due to an incomplete understanding of the disease’s etiology. Alpha-synuclein (α-syn) has become a point of focus in PD due to its connection to both familial and idiopathic cases—specifically its localization to Lewy bodies (LBs), a pathological hallmark of PD. Within this review, we will present a comprehensive overview of the data linking synuclein-associated Lewy pathology with intracellular dysfunction. We first present the alterations in neuronal proteins and transcriptome associated with LBs in postmortem human PD tissue. We next compare these findings to those associated with LB-like inclusions initiated by in vitro exposure to α-syn preformed fibrils (PFFs) and highlight the profound and relatively unique reduction of brain-derived neurotrophic factor (BDNF) in this model. Finally, we discuss the multitude of ways in which BDNF offers the potential to exert disease-modifying effects on the basal ganglia. What remains unknown is the potential for BDNF to mitigate inclusion-associated dysfunction within the context of synucleinopathy. Collectively, this review reiterates the merit of using the PFF model as a tool to understand the physiological changes associated with LBs, while highlighting the neuroprotective potential of harnessing endogenous BDNF.Kathryn M. MillerNatosha M. MercadoCaryl E. SortwellNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-9 (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 Kathryn M. Miller Natosha M. Mercado Caryl E. Sortwell Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
description	Abstract The lack of disease-modifying treatments for Parkinson’s disease (PD) is in part due to an incomplete understanding of the disease’s etiology. Alpha-synuclein (α-syn) has become a point of focus in PD due to its connection to both familial and idiopathic cases—specifically its localization to Lewy bodies (LBs), a pathological hallmark of PD. Within this review, we will present a comprehensive overview of the data linking synuclein-associated Lewy pathology with intracellular dysfunction. We first present the alterations in neuronal proteins and transcriptome associated with LBs in postmortem human PD tissue. We next compare these findings to those associated with LB-like inclusions initiated by in vitro exposure to α-syn preformed fibrils (PFFs) and highlight the profound and relatively unique reduction of brain-derived neurotrophic factor (BDNF) in this model. Finally, we discuss the multitude of ways in which BDNF offers the potential to exert disease-modifying effects on the basal ganglia. What remains unknown is the potential for BDNF to mitigate inclusion-associated dysfunction within the context of synucleinopathy. Collectively, this review reiterates the merit of using the PFF model as a tool to understand the physiological changes associated with LBs, while highlighting the neuroprotective potential of harnessing endogenous BDNF.
format	article
author	Kathryn M. Miller Natosha M. Mercado Caryl E. Sortwell
author_facet	Kathryn M. Miller Natosha M. Mercado Caryl E. Sortwell
author_sort	Kathryn M. Miller
title	Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
title_short	Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
title_full	Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
title_fullStr	Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
title_full_unstemmed	Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor
title_sort	synucleinopathy-associated pathogenesis in parkinson’s disease and the potential for brain-derived neurotrophic factor
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f5cdec01b89e4bc586532d9150c98dee
work_keys_str_mv	AT kathrynmmiller synucleinopathyassociatedpathogenesisinparkinsonsdiseaseandthepotentialforbrainderivedneurotrophicfactor AT natoshammercado synucleinopathyassociatedpathogenesisinparkinsonsdiseaseandthepotentialforbrainderivedneurotrophicfactor AT carylesortwell synucleinopathyassociatedpathogenesisinparkinsonsdiseaseandthepotentialforbrainderivedneurotrophicfactor
_version_	1718391286600302592

Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor

Ejemplares similares