Project Summary:
Parkinson’s disease (PD) is a severe, progressive neurodegenerative condition affecting 8.5 million people globally. Its pathological hallmark is the loss of dopaminergic (DA) neurons and the presence of α-synuclein aggregates in the substantia nigra pars compacta (SNc). Sadly, there is no cure for PD. Current treatments primarily focus on symptomatic relief through dopaminergic medications and deep brain stimulation, and none of these treatments stops neurodegeneration. In 2019, the World Health Organization estimated that 8.5 million individuals live with PD, and PD-related fatalities climbed up to 329,000. PD-affected people in the U.S. are estimated to be approximately one million, which may rise to 1.2 million by 2030, and the PD economic burden in the United States is estimated at $52 billion annually. In Wisconsin, the situation is not any better: over 15,000 individuals are living with PD, with a clear trend of increase due to the aging population. Despite considerable advances in the field, the molecular mechanisms driving DA neuron death remain elusive. Given this significant gap, there is an urgent need to understand disease-modifying factors, which is crucial to developing novel drug targets for new therapies.
This project aims to test a novel drug target to attenuate PD progression by focusing on SARM1 (Sterile Alpha and TIR Motif Containing 1), a newly identified NAD+ hydrolase. The researchers hypothesize that SARM1 plays an important role in dopaminergic axonal degeneration and neuron death, and they will test this hypothesis by SARM1 genetic inactivation in PD mouse models.
If successful, this work will identify a new drug target to stop DA neuron death at the root cause of PD.