Current insights into pathogenesis of Parkinson's disease: Approach to mevalonate pathway and protective role of statins

Abstract

Although Parkinson's disease (PD) is considered as the second most common life threatening age-related neurodegenerative disorder, but the underlying mechanisms for pathogenesis of PD are remained to be fully found. However, a complex relationship between genetic and environmental predisposing factors are involved in progression of PD. Dopaminergic neuronal cell death caused by mutations and accumulation of α-synuclein in Lewy bodies and neurites was suggested as the main strategy for PD, but current studies have paid attention to the role of mevalonate pathway in incidence of neurodegenerative diseases including PD. The discovery may change the therapeutic protocols from symptomatic treatment by dopamine precursors and agonists to neurodegenerative process halting drugs. Moreover, the downstream metabolites of mevalonate pathway may be used as diagnostic biomarkers for early diagnosis of PD. Statins, as cholesterol lowering drugs, may ameliorate the enzyme complex dysfunction, a key step in the progression of the neurodegenerative disorders, oxidative stress-induced damage and neuro-inflammation. Statins exert the neuroprotective effects on striatal dopaminergic neurons through blocking the mevalonate pathway. In the present review, we have focused on the new approaches to pathogenesis of PD regarding to mevalonate pathway, in addition to the previous understood mechanisms for the disease. It tries to elucidate the novel findings about PD for the development of future diagnostic and therapeutic strategies. Moreover, we explain the controversial role of statins in improvement or progression of PD and the position of these drugs in neuroprotection in PD patients.

Keywords: Mevalonate pathway; Neurodegeneration; Parkinson’s disease; Statins.