Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities
The underlying pathophysiology of Parkinson's disease is complex, but mitochondrial dysfunction has an established and prominent role. This is supported by an already large and rapidly growing body of evidence showing that the role of mitochondrial (dys)function is central and multifaceted. How...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.615461/full |
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| author | Jannik Prasuhn Jannik Prasuhn Jannik Prasuhn Ryan L. Davis Ryan L. Davis Kishore R. Kumar Kishore R. Kumar |
| author_facet | Jannik Prasuhn Jannik Prasuhn Jannik Prasuhn Ryan L. Davis Ryan L. Davis Kishore R. Kumar Kishore R. Kumar |
| author_sort | Jannik Prasuhn |
| collection | DOAJ |
| description | The underlying pathophysiology of Parkinson's disease is complex, but mitochondrial dysfunction has an established and prominent role. This is supported by an already large and rapidly growing body of evidence showing that the role of mitochondrial (dys)function is central and multifaceted. However, there are clear gaps in knowledge, including the dilemma of explaining why inherited mitochondriopathies do not usually present with parkinsonian symptoms. Many aspects of mitochondrial function are potential therapeutic targets, including reactive oxygen species production, mitophagy, mitochondrial biogenesis, mitochondrial dynamics and trafficking, mitochondrial metal ion homeostasis, sirtuins, and endoplasmic reticulum links with mitochondria. Potential therapeutic strategies may also incorporate exercise, microRNAs, mitochondrial transplantation, stem cell therapies, and photobiomodulation. Despite multiple studies adopting numerous treatment strategies, clinical trials to date have generally failed to show benefit. To overcome this hurdle, more accurate biomarkers of mitochondrial dysfunction are required to detect subtle beneficial effects. Furthermore, selecting study participants early in the disease course, studying them for suitable durations, and stratifying them according to genetic and neuroimaging findings may increase the likelihood of successful clinical trials. Moreover, treatments involving combined approaches will likely better address the complexity of mitochondrial dysfunction in Parkinson's disease. Therefore, selecting the right patients, at the right time, and using targeted combination treatments, may offer the best chance for development of an effective novel therapy targeting mitochondrial dysfunction in Parkinson's disease. |
| first_indexed | 2024-12-21T12:07:18Z |
| format | Article |
| id | doaj.art-86a2b4a2d5e4467dbab79b418ae59064 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T12:07:18Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-86a2b4a2d5e4467dbab79b418ae590642022-12-21T19:04:41ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-01-01810.3389/fcell.2020.615461615461Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and OpportunitiesJannik Prasuhn0Jannik Prasuhn1Jannik Prasuhn2Ryan L. Davis3Ryan L. Davis4Kishore R. Kumar5Kishore R. Kumar6Institute of Neurogenetics, University of Lübeck, Lübeck, GermanyDepartment of Neurology, University Medical Center Schleswig-Holstein, Lübeck, GermanyCenter for Brain, Behavior, and Metabolism, University of Lübeck, Lübeck, GermanyDepartment of Neurogenetics, Kolling Institute, University of Sydney and Northern Sydney Local Health District, Sydney, NSW, AustraliaDepartment of Neurogenetics, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, AustraliaMolecular Medicine Laboratory and Department of Neurology, Concord Repatriation General Hospital, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, AustraliaKinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaThe underlying pathophysiology of Parkinson's disease is complex, but mitochondrial dysfunction has an established and prominent role. This is supported by an already large and rapidly growing body of evidence showing that the role of mitochondrial (dys)function is central and multifaceted. However, there are clear gaps in knowledge, including the dilemma of explaining why inherited mitochondriopathies do not usually present with parkinsonian symptoms. Many aspects of mitochondrial function are potential therapeutic targets, including reactive oxygen species production, mitophagy, mitochondrial biogenesis, mitochondrial dynamics and trafficking, mitochondrial metal ion homeostasis, sirtuins, and endoplasmic reticulum links with mitochondria. Potential therapeutic strategies may also incorporate exercise, microRNAs, mitochondrial transplantation, stem cell therapies, and photobiomodulation. Despite multiple studies adopting numerous treatment strategies, clinical trials to date have generally failed to show benefit. To overcome this hurdle, more accurate biomarkers of mitochondrial dysfunction are required to detect subtle beneficial effects. Furthermore, selecting study participants early in the disease course, studying them for suitable durations, and stratifying them according to genetic and neuroimaging findings may increase the likelihood of successful clinical trials. Moreover, treatments involving combined approaches will likely better address the complexity of mitochondrial dysfunction in Parkinson's disease. Therefore, selecting the right patients, at the right time, and using targeted combination treatments, may offer the best chance for development of an effective novel therapy targeting mitochondrial dysfunction in Parkinson's disease.https://www.frontiersin.org/articles/10.3389/fcell.2020.615461/fullParkinson's diseasemitochondriatherapymitochondrial dysfunctionneurodegeneration |
| spellingShingle | Jannik Prasuhn Jannik Prasuhn Jannik Prasuhn Ryan L. Davis Ryan L. Davis Kishore R. Kumar Kishore R. Kumar Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities Frontiers in Cell and Developmental Biology Parkinson's disease mitochondria therapy mitochondrial dysfunction neurodegeneration |
| title | Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities |
| title_full | Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities |
| title_fullStr | Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities |
| title_full_unstemmed | Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities |
| title_short | Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities |
| title_sort | targeting mitochondrial impairment in parkinson s disease challenges and opportunities |
| topic | Parkinson's disease mitochondria therapy mitochondrial dysfunction neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.615461/full |
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