Parkinson’s disease (PD) is an age-related movement disorder that currently affects one million people in the U.S. and 10 million people worldwide, making it one of the most prevalent neurodegenerative diseases. PD causes resting tremors, altered walking and gait, limb rigidity, and other issues with motor function. In addition, a majority of individuals develop cognitive impairments and other non-motor symptoms, which often impact their daily lives even more than the motor symptoms. These non-motor symptoms are caused by impacts of the disease on neuronal synapses, the functional contacts between neurons.

The National Institutes of Health (NIH) recently awarded a grant to MBL Senior Scientist Jennifer Morgan (Eugene Bell Center for Regenerative Biology and Tissue Engineering) to further her research on the impacts of PD on neuronal synapses.

PD is strongly linked to the aberrant aggregation of a synaptic protein called α-synuclein. With this project, Morgan’s lab will first determine how α-synuclein aggregates, isolated from human brains post mortem, affect synaptic processes.

Over the past decade, the Morgan lab has developed and implemented the sea lamprey (Petromyzon marinus) as a model for studying how α-synuclein impacts synapse structure and function. This project will continue to take advantage of the unique features of the sea lamprey’s giant reticulospinal synapses, which permit detailed analyses of synaptic structure and function using high-resolution imaging and electrophysiology approaches.

A second goal is to test several α-synuclein inhibitors, including small-molecule drug compounds, to determine if they can ameliorate or reverse the deleterious impacts of α-synuclein aggregates at synapses. Thus, the study will also provide critical knowledge for designing targeted therapies aimed at improving synapse function in PD. Because α-synuclein aggregation is associated with dementia with Lewy bodies, as well as some variants of Alzheimer’s disease, these studies also have wider implications for understanding of a number of common neurodegenerative diseases.

This research is co-funded by The National Institute of Neurological Disorders and Stroke (NINDS) and The National Institute on Aging (NIA).

EM image of a sea lamprey synapse. Credit: Paul Oliphant, Morgan lab
Electron microscope image of a sea lamprey synapse. Credit: Paul Oliphant, Morgan lab