Curcumin pre-treatment may protect against mitochondrial damage in LRRK2-mutant Parkinson's disease and healthy control fibroblasts
| Autor: | Shameemah Abrahams, Soraya Bardien, Hayley Christy Miller, Carl Lombard, Francois H. van der Westhuizen |
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| Rok vydání: | 2021 |
| Předmět: |
Paraquat
0301 basic medicine Parkinson's disease QH301-705.5 Biophysics QD415-436 Pharmacology medicine.disease_cause Biochemistry Neuroprotection 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Biology (General) chemistry.chemical_classification Reactive oxygen species business.industry Neurodegeneration Turmeric medicine.disease LRRK2 030104 developmental biology chemistry Oxidative stress 030220 oncology & carcinogenesis Curcumin Mitochondrial function business |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 27, Iss, Pp 101035-(2021) |
| ISSN: | 2405-5808 |
| DOI: | 10.1016/j.bbrep.2021.101035 |
| Popis: | Mitochondrial dysfunction has been proposed as one of the pathobiological underpinnings in Parkinson's disease. Environmental stressors, such as paraquat, induce mitochondrial dysfunction and promote reactive oxygen species production. Targeting oxidative stress pathways could prevent mitochondrial dysfunction and thereby halt the neurodegeneration in Parkinson's disease. Since curcumin is touted as an antioxidant and neuroprotective agent, the aim of this study was to investigate if curcumin is a suitable therapy to target mitochondrial dysfunction in Parkinson's disease using a paraquat-toxicity induced model in fibroblasts from LRRK2-mutation positive Parkinson's disease individuals and healthy controls. The fibroblasts were exposed to five treatment groups, (i) untreated, (ii) curcumin only, (iii) paraquat only, (iv) pre-curcumin group: with curcumin for 2hr followed by paraquat for 24hr and (v) post-curcumin group: with paraquat for 24hr followed by curcumin for 2hr. Mitochondrial function was determined by measuring three parameters of mitochondrial respiration (maximal respiration, ATP-associated respiration, and spare respiratory capacity) using the Seahorse XFe96 Extracellular Flux Analyzer. As expected, paraquat effectively disrupted mitochondrial function for all parameters. Pre-curcumin treatment improved maximal and ATP-associated respiration whereas, post-curcumin treatment had no effect. These findings indicate that curcumin may be most beneficial as a pre-treatment before toxin exposure, which has implications for its therapeutic use. These promising findings warrant future studies testing different curcumin dosages, exposure times and curcumin formulations in larger sample sizes of Parkinson's disease and control participants. |
| Databáze: | OpenAIRE |
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