Maintenance of Nerve Terminals by Local Synthesis of Proteins in Axons

Function of the nervous system depends on maintaining the connections between neurons throughout life. Loss of these synaptic connections is thought to be one of the early events in neurodegenerative diseases like Parkinson's disease. The processes that connect neurons extend for long distances from the neuronal cell body. Over the past few years it has become clear that some proteins are made locally within these neuronal processes. This provides these synaptic connections with autonomy to rapidly respond to environmental cues without signaling to the cell body. We are only just now beginning to determine which proteins are made in these processes and the functional implications of this localized protein synthesis. Our recent data indicate that gene products that are mutated in familial forms of Parkinson's disease are locally made in nerve processes. In these studies, we will determine the signals that induce production of these proteins in nerve terminals and the potential function of these gene products in nerve terminals. Together, these studies may help to understand how loss of function of these gene products contributes to the degeneration of dopaminergic nerve terminals that occurs early on in Parkinson's disease.