Curcumin pre-treatment may protect against mitochondrial damage in LRRK2-mutant Parkinson's disease and healthy control fibroblasts

被引：17

作者：

Abrahams, Shameemah ^{[1
]}

Miller, Hayley C. ^{[2
]}

Lombard, Carl ^{[3
,4
]}

van der Westhuizen, Francois H. ^{[2
]}

Bardien, Soraya ^{[1
]}

机构：

[1] Stellenbosch Univ, Div Mol Biol & Human Genet, Fac Med & Hlth Sci, Cape Town, South Africa

[2] North West Univ, Human Metabol, Fac Nat Sci, Potchefstroom, South Africa

[3] Stellenbosch Univ, Fac Med & Hlth Sci, Div Epidemiol & Biostat, Dept Global Hlth, Cape Town, South Africa

[4] South African Med Res Council, Biostat Unit, Cape Town, South Africa

来源：

BIOCHEMISTRY AND BIOPHYSICS REPORTS | 2021年 / 27卷

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

Turmeric; Mitochondrial function; Paraquat; Oxidative stress; PARAQUAT;

D O I：

10.1016/j.bbrep.2021.101035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 neuro-protective 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 param-eters. 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.

引用

页数：6