Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies
Parkinson’s disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown etiology, with both genetics and environment playing important roles. Over the past 25 years, however, g...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.01381/full |
| _version_ | 1818014547624067072 |
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| author | Kirsten Ebanks Kirsten Ebanks Patrick A. Lewis Patrick A. Lewis Rina Bandopadhyay Rina Bandopadhyay |
| author_facet | Kirsten Ebanks Kirsten Ebanks Patrick A. Lewis Patrick A. Lewis Rina Bandopadhyay Rina Bandopadhyay |
| author_sort | Kirsten Ebanks |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown etiology, with both genetics and environment playing important roles. Over the past 25 years, however, genetic analysis of patients with familial history of Parkinson’s and, latterly, genome wide association studies (GWAS) have provided significant advances in our understanding of the causes of the disease. These genetic insights have uncovered pathways that are affected in both genetic and sporadic forms of PD. These pathways involve oxidative stress, abnormal protein homeostasis, mitochondrial dysfunction, and lysosomal defects. In addition, newly identified PD genes and GWAS nominated genes point toward synaptic changes involving vesicles. This review will highlight the genes that contribute PD risk relating to intracellular vesicle trafficking and their functional consequences. There is still much to investigate on this newly identified and converging pathway of vesicular dynamics and PD, which will aid in better understanding and suggest novel therapeutic strategies for PD patients. |
| first_indexed | 2024-04-14T06:46:03Z |
| format | Article |
| id | doaj.art-ae88ab0e90164e6a9c7d4fc3233621ef |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-14T06:46:03Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-ae88ab0e90164e6a9c7d4fc3233621ef2022-12-22T02:07:10ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-01-011310.3389/fnins.2019.01381504220Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic StudiesKirsten Ebanks0Kirsten Ebanks1Patrick A. Lewis2Patrick A. Lewis3Rina Bandopadhyay4Rina Bandopadhyay5Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, United KingdomDepartment of Clinical and Motor Neuroscience, UCL Queen Square Institute of Neurology, University College London, London, United KingdomSchool of Pharmacy, University of Reading, Reading, United KingdomDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, United KingdomReta Lila Weston Institute, UCL Queen Square Institute of Neurology, University College London, London, United KingdomDepartment of Clinical and Motor Neuroscience, UCL Queen Square Institute of Neurology, University College London, London, United KingdomParkinson’s disease (PD) is a common age-related neurodegenerative disorder with disabling motor symptoms and no available disease modifying treatment. The majority of the PD cases are of unknown etiology, with both genetics and environment playing important roles. Over the past 25 years, however, genetic analysis of patients with familial history of Parkinson’s and, latterly, genome wide association studies (GWAS) have provided significant advances in our understanding of the causes of the disease. These genetic insights have uncovered pathways that are affected in both genetic and sporadic forms of PD. These pathways involve oxidative stress, abnormal protein homeostasis, mitochondrial dysfunction, and lysosomal defects. In addition, newly identified PD genes and GWAS nominated genes point toward synaptic changes involving vesicles. This review will highlight the genes that contribute PD risk relating to intracellular vesicle trafficking and their functional consequences. There is still much to investigate on this newly identified and converging pathway of vesicular dynamics and PD, which will aid in better understanding and suggest novel therapeutic strategies for PD patients.https://www.frontiersin.org/article/10.3389/fnins.2019.01381/fullParkinson’s diseasegeneticsgenome wide association studiesvesicular dysfunctionlysosomal dysfunctionalpha-synuclein |
| spellingShingle | Kirsten Ebanks Kirsten Ebanks Patrick A. Lewis Patrick A. Lewis Rina Bandopadhyay Rina Bandopadhyay Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies Frontiers in Neuroscience Parkinson’s disease genetics genome wide association studies vesicular dysfunction lysosomal dysfunction alpha-synuclein |
| title | Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies |
| title_full | Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies |
| title_fullStr | Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies |
| title_full_unstemmed | Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies |
| title_short | Vesicular Dysfunction and the Pathogenesis of Parkinson’s Disease: Clues From Genetic Studies |
| title_sort | vesicular dysfunction and the pathogenesis of parkinson s disease clues from genetic studies |
| topic | Parkinson’s disease genetics genome wide association studies vesicular dysfunction lysosomal dysfunction alpha-synuclein |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.01381/full |
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