Fig. 3.

Mitochondrial involvement in Parkinson’s disease (PD) and the potential therapeutic efficacy of creatine supplementation. (1) PD is characterized by impaired activity of complex I in the ETC of mitochondria. In support of a mitochondrially based etiology in PD, administration of the mitochondrial-specific neurotoxin, MPTP, in animal models, inhibits complex I of the ETC and leads to PD-like pathogenesis. Suppression and/or inhibition of complex I of the ETC lowers overall mitochondrial ATP production and consequently diminishes the ATP (dashed lines) that can be potentially utilized for PCr generation by the MtCK. 2) Additionally, impaired ETC function increases ROS production to induce an octameric-to-dimeric shift of MtCK rendering it an inactive state and elevated ROS will also reduce cytosolic CK activity. (3) Data have shown that creatine supplementation is an efficacious treatment paradigm for PD animal models, but the exact molecular mechanisms are not fully elucidated. However, exogenous creatine appears to improve overall cellular bioenergetics and mitochondrial function by enhancing the PCr pool and this reduces the neuronal cell loss associated with PD pathogenesis. Given the promising results of creatine in animal models of PD, a phase III clinical study of creatine supplementation in PD patients is now underway