Cocoa beans improve mitochondrial biogenesis via PPARγ/PGC1α dependent signalling pathway in MPP+ intoxicated human neuroblastoma cells (SHSY5Y).

Polyphenols are shown to protect from or delay the progression of chronic neurodegenerative diseases.
Mitochondrial dysfunction plays a key role in the pathogenesis of Parkinson’s disease (PD). This study
was aims to gain insight into the role of ahydroalcoholic extract of cocoa (standardised for epicatechin
content) on mitochondrial biogenesis in MPP+ intoxicated human neuroblastoma cells (SHSY5Y). The
effects of cocoa on PPARγ, PGC1α, Nrf2 and TFAM protein expression and mitochondrial membrane
potential were evaluated. A pre-exposure to cocoa extract decreased reactive oxygen species formation
and restored mitochondrial membrane potential. The cocoa extract was found to up-regulate the
expression of PPARγ and the downstream signalling proteins PGC1α, Nrf2 and TFAM. It increased the
expression of the anti-apoptotic protein BCl2 and increased superoxide dismutase activity. Further, the
cocoa extract down-regulated the expression of mitochondria fission 1 (Fis1) and up-regulated the
expression of mitochondria fusion 2 (Mfn2) proteins, suggesting an improvement in mitochondrial
functions in MPP+ intoxicated cells upon treatment with cocoa. Interestingly, cocoa up-regulates the
expression of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis. No change in the
expression of PPARγ on treatment with cocoa extract was observed when the cells were pre-treated with
PPARγ antagonist GW9662. This data suggests that cocoa mediates mitochondrial biogenesis via a
PPARγ/PGC1α dependent signalling pathway and also has the ability to improve dopaminergic functions
by increasing tyrosine hydroxylase expression. Based on our data, we propose that a cocoa bean extract
and products thereof could be used as potential nutritional supplements for neuroprotection in PD.