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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-04-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-021-00179-6 |
| _version_ | 1797641246754209792 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T13:42:51Z |
| format | Article |
| id | doaj.art-f5cdec01b89e4bc586532d9150c98dee |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T13:42:51Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-f5cdec01b89e4bc586532d9150c98dee2023-11-02T11:36:35ZengNature Portfolionpj Parkinson's Disease2373-80572021-04-01711910.1038/s41531-021-00179-6Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factorKathryn M. Miller0Natosha M. Mercado1Caryl E. Sortwell2Department of Translational Neuroscience, College of Human Medicine, Michigan State UniversityDepartment of Translational Neuroscience, College of Human Medicine, Michigan State UniversityDepartment of Translational Neuroscience, College of Human Medicine, Michigan State UniversityAbstract 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.https://doi.org/10.1038/s41531-021-00179-6 |
| spellingShingle | Kathryn M. Miller Natosha M. Mercado Caryl E. Sortwell Synucleinopathy-associated pathogenesis in Parkinson’s disease and the potential for brain-derived neurotrophic factor npj Parkinson's Disease |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41531-021-00179-6 |
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