Restoration of mitochondrial function by activation of the NAD+/Sirtuin pathway to treat PD
Parkinson’s Disease (PD) is a debilitating neurodegenerative disease for which there is no cure. The cardinal motor symptoms of PD are caused by the massive loss of neurons in a region of the brain called the substantia nigra pars compacta (SNc), that use dopamine as a chemical messenger (Giguère et al., 2018). Evidence has converged in recent years on mitochondrial dysfunction as a central mechanism underlying the pathogenesis of PD. Mitochondria are the energy powerhouses of cells, producing energy in the form of ATP molecules.
Although a number of hypotheses have been raised to explain why SNc neurons are particularly susceptible to mitochondrial dysfunction and die in PD, recent work from the Trudeau laboratory has provided strong support for a novel hypothesis suggesting that SNc dopamine neurons are most at risk because they are neurons with an exceptionally large number of connections with other brain cells, leading to very high energy demands (Pacelli et al., 2015). The very high mitochondrial activity required to produce this energy would make SNc neurons vulnerable because this would come with a very high basal level of oxidative stress, gradually leading to impaired cell function and death. Identifying new strategies to improve mitochondrial efficiency is therefore an important aim to discover new treatments for PD.
One potentially promising approach would be to target the nicotinamide adenine dinucleotide (NAD+) pathway.
Louis-Eric Trudeau , Université de Montréal
Partners and Donors
Henry and Berenice Kaufmann Foundation