A mitochondrial uncoupler prodrug protects dopaminergic neurons and improves functional outcome in a mouse model of Parkinson’s disease
| Autor: | Dong Liu, John G. Geisler, Mark P. Mattson, William Fang, Joshua C. Johnson, Krisztina Marosi, Yuki Kishimoto, Joshua Halpern |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Aging Parkinson's disease Uncoupling Agents Substantia nigra Pharmacology Mitochondrion 03 medical and health sciences 0302 clinical medicine Dopamine Animals Medicine Prodrugs Oxidopamine Neuroinflammation Cell Death Microglia business.industry Dopaminergic Neurons General Neuroscience Dopaminergic Parkinson Disease medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure nervous system Neurology (clinical) Geriatrics and Gerontology 2 4-Dinitrophenol business 030217 neurology & neurosurgery Developmental Biology medicine.drug |
| Zdroj: | Neurobiology of Aging. 85:123-130 |
| ISSN: | 0197-4580 |
| DOI: | 10.1016/j.neurobiolaging.2019.09.011 |
| Popis: | Dopaminergic neuronal cell loss in the substantia nigra is responsible for the motor symptoms that are the clinical hallmark of Parkinson’s disease (PD). As of yet there are no treatments that slow or prevent the degeneration of dopaminergic neurons in PD patients. Here we tested the hypothesis that dopaminergic neurons can be protected by treatment with the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) and the novel DNP prodrug MP201. We found that mice treated with low doses of DNP and MP201 were protected against motor dysfunction and dopamine neuron loss in the 6-hydroxydopamine PD model, with MP201 being more efficacious than DNP. Amelioration of motor deficits and dopamine neuron loss by MP201 treatment was associated with reductions in microglial and astrocyte activation and neuroinflammation. These preclinical findings suggest the potential application of mitochondrial uncoupling agents such as MP201 as disease-modifying therapies for PD. |
| Databáze: | OpenAIRE |
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