Parkinson's disease (PD) is the second most prevalent
neurodegenerative disease and this study underlines the significance of a small molecule
glyceryl tribenzoate (GTB), a FDA approved
food additive, in preventing parkinsonian pathologies in
MPTP-induced animal models. The study conducted in
MPTP-induced mice demonstrated dose-dependent protection of nigral
tyrosine hydroxylase (TH) and striatal
dopamine level by GTB oral treatment and the optimum dose was found to be 50 mg/kg/d. In the next phase, the study was carried out in
MPTP-injected hemiparkinsonian monkeys, which recapitulate better clinical
parkinsonian syndromes. GTB inhibited
MPTP-driven induction of glial
inflammation, which was evidenced by reduced level of GTP-p21Ras and phospho-p65 in SN of monkeys. It led to decreased expression of inflammatory markers such as IL-1β and iNOS. Simultaneously, GTB oral treatment protected nigral TH cells, striatal
dopamine, and improved motor behaviour of hemiparkinsonian monkeys. Presence of
sodium benzoate, a GTB metabolite and a FDA-approved
drug for
urea cycle disorders and
glycine encephalopathy, in the brain suggests that the
neuroprotective effect imparted by GTB might be mediated by
sodium benzoate. Although the mechanism of action of GTB is poorly understood, the study sheds light on the therapeutic possibility of a
food additive GTB in PD.