Abstract

A variety of age-linked neurodegenerative diseases affect an increasingly large number of people and we have limited understanding of the processes that lead to these disorders. Parkinson’s Disease (PD) is one of the most common neurodegenerative diseases and it features a selective loss of dopamine neurons that have a critical role in regulating movement and reward processing among other brain functions. It has been observed that loss of the axon – cellular compartment that contains the sites of dopamine release – often precedes the loss of the cell body. Furthermore, some of the genetic forms of PD are caused by mutations in proteins localized at the release site, pointing to the machinery that regulates dopamine release as a potential source of vulnerability. We compared the composition of dopamine release machinery to that of the principal excitatory neurotransmitter glutamate and found significant differences, including the reduced expression of a neuroprotective chaperone cysteine string protein-alpha (CSPa). This project aims to study the role of CSPa in normal dopamine release, its expression over aging and in dopamine neuron populations with different levels of resilience. We also hope to reveal mechanistic links between presynaptic function and neuronal survival.