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

Abstract

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 XF e 96 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.

A novel curcumin oil solution can better alleviate the motor activity defects and neuropathological damage of a Parkinson’s disease mouse model

“…However, this study has a limitation in that the mechanism of action of this curcumin oil solution is not explained. As there have been many reports about curcumin against PD, we assume that it could possibly reverse neuron degeneration in SNc and the dopaminergic system disorders in brain according to our findings, improve neuronal mitochondrial function (Abrahams et al, 2021), prevent α-synuclein aggregation (Chetty et al, 2021) or regulate some immune and inflammatory factors (Mollazadeh et al, 2019), which will be verified in our next study. Moreover, about the drug curcumin, we just evaluated its distribution in vivo and the brain using the In vivo Imaging System but failed to effectively discover the drug metabolism and processes across the blood-brain barrier.…”

“…In previous studies, curcumin has been evaluated to improve or prevent movement disorders in PD, but the evidence is not comprehensive enough (Bhat et al, 2019;Rabiei et al, 2019;Abrahams et al, 2021;El Nebrisi, 2021). In this study, through behavioral tests including the OFT, rotarod test, pole test, and automated gait analysis, we provided comprehensive and solid evidence regarding the effect of our novel curcumin oil solution on the prevention of movement disorders caused by MPTP toxicity.…”

Neuroprotective Activities of Curcumin in Parkinson’s Disease: A Review of the Literature

“…A critical unmet need in the management of PD is the discovery of new approaches that could slow, stop, or ideally reverse, the process of neurodegeneration. Curcumin’s neuroprotective potential has been demonstrated in several recent studies using various animal models of Parkinson’s disease [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. For instance, Zbarsky described the protective effects of curcumin on the number of TH-positive neurons as well as on striatal DA level and its metabolites; dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) against 6-hydroxydopmine (6-OHDA) induced neurodegeneration in animal models of PD [ 71 ].…”

Curcumin-driven reprogramming of the gut microbiota and metabolome ameliorates motor deficits and neuroinflammation in a mouse model of Parkinson’s disease

“…A large body of cell and animal research has investigated the positive effects of CUR in PD ( Qualls et al., 2014 ; van der Merwe et al., 2017 ; Sharma and Nehru, 2018 ; Dehghani et al., 2020 ; Abrahams et al., 2021 ). For example, seven weeks of dietary supplementation with CUR were previously shown to prevent the loss of DA neurons in the SNpc and striatum in MPTP mice ( He et al., 2015 ).…”