Neuroprotective Effects of Betulin in Pharmacological and Transgenic C. elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly.It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Currently, therapeutics for PD provide satisfactory symptom relief, but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process. Betulin is derived from the bark of birch trees, and possesses anti-cancer, antimicrobial, and antiinflammatory properties. The aim of the present study was to evaluate the potential for betulin to ameliorate PD features in Caenorhabditis elegans (C. elegans) models. We demonstrated that betulin diminished α-syn accumulation in the transgenic C. elegans model. Betulin also reduced 6-hydroxydopamine-induced dopaminergic neuron degeneration, reduced foodsensing behavioral abnormalities, and reversed life-span decreases in a pharmacological C. elegans model. Moreover, we found that enhancement of proteasomes activity by promoting rpn1 expression and down-regulation of the apoptosis pathway gene, egl-1, may be the molecular mechanism for betulin-mediated protection against PD pathology. Together, these findings support betulin as a possible treatment for PD and encourage further investigations of betulin as an anti-neurodegenerative agent.