ArticleNeurochemistry international2017
Long-term oral kinetin does not protect against α-synuclein-induced neurodegeneration in rodent models of Parkinson's disease.
Article in Neurochemistry international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- UQCRC1 deficiency impairs mitophagy via PINK1-dependent mechanisms in Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Targeting mitophagy in neurodegenerative diseases.Nature reviews. Drug discovery · 2025Review
- Pharmacological PINK1 activation ameliorates Pathology in Parkinson's Disease models.Research square · 2024Article
- Cerebellar activity in PINK1 knockout rats during volitional gait.Brain communications · 2024Article
- Parkinson's disease relevant pathological features are manifested in male Pink1/Parkin deficient rats.Brain, behavior, & immunity - health · 2023Article
- Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease, with insights intoZoological research · 2023Review
- Targeting Mitochondria as a Therapeutic Approach for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- Prospects for the Development of Pink1 and Parkin Activators for the Treatment of Parkinson's Disease.Pharmaceutics · 2022Review
- Mitigation of age-dependent accumulation of defective mitochondrial genomes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Therapeutic targeting of mitophagy in Parkinson's disease.Biochemical Society transactions · 2022Review
- Mitochondria in neurodegeneration.Current opinion in physiology · 2022Article
- PINK1/Parkin Pathway Activation for Mitochondrial Quality Control - Which Is the Best Molecular Target for Therapy?Frontiers in aging neuroscience · 2022Review
- Relevance of Autophagy and Mitophagy Dynamics and Markers in Neurodegenerative Diseases.Biomedicines · 2021Review
- Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities.Cell death and differentiation · 2021Review
- Identifying Therapeutic Agents for Amelioration of Mitochondrial Clearance Disorder in Neurons of Familial Parkinson Disease.Stem cell reports · 2020Article
- A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling.iScience · 2020Article
- Targeting Mitochondrial Impairment in Parkinson's Disease: Challenges and Opportunities.Frontiers in cell and developmental biology · 2020Review
- To be or not to be pink(1): contradictory findings in an animal model for Parkinson's disease.Brain communications · 2019Article
- Current perspective of mitochondrial biology in Parkinson's disease.Neurochemistry international · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in the mitochondrial kinase PTEN-induced putative kinase 1 (PINK1) cause Parkinson's disease (PD), likely by disrupting PINK1's kinase activity. Although the mechanism(s) underlying how this loss of activity causes degeneration remains unclear, increasing PINK1 activity may therapeutically benefit some forms of PD. However, we must first learn whether restoring PINK1 function prevents degeneration in patients harboring PINK1 mutations, or whether boosting PINK1 function can offer protection in more common causes of PD. To test these hypotheses in preclinical rodent models of PD, we used kinetin triphosphate, a small-molecule that activates both wild-type and mutant forms of PINK1, which affects mitochondrial function and protects neural cells in culture. We chronically fed kinetin, the precursor of kinetin triphosphate, to PINK1-null rats in which PINK1 was reintroduced into their midbrain, and also to rodent models overexpressing α-synuclein. The highest tolerated dose of oral kinetin increased brain levels of kinetin for up to 6 months, without adversely affecting the survival of nigrostriatal dopamine neurons. However, there was no degeneration of midbrain dopamine neurons lacking PINK1, which precluded an assessment of neuroprotection and raised questions about the robustness of the PINK1 KO rat model of PD. In two rodent models of α-synuclein-induced toxicity, boosting PINK1 activity with oral kinetin provided no protective effects. Our results suggest that oral kinetin is unlikely to protect against α-synuclein toxicity, and thus fail to provide evidence that kinetin will protect in sporadic models of PD. Kinetin may protect in cases of PINK1 deficiency, but this possibility requires a more robust PINK1 KO model that can be validated by proof-of-principle genetic correction in adult animals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.