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Funded Studies

Investigating Alpha-synuclein Clumping in the Organoid Model of Parkinson's Disease

Study Rationale:
Alpha-synuclein -- a sticky protein that clumps in the brains of people with Parkinson's disease (PD) -- is a major target for the development of therapies for PD. Alpha-synuclein clumping and PD progression are strongly linked. Since it is unclear how these clumps form and contribute to disease progression, preventing or reducing alpha-synuclein clumping is important. Researchers still do not know what causes changes in alpha-synuclein structure that prompt its clumping in the brain.

We hypothesize that both genetic and environmental factors affect the structure of alpha-synuclein and its ability to clump.

Study Design:
In this project, we aim to define how and when changes in alpha-synuclein cause it to clump. To accomplish this, we will use organoids, brain-like structures containing dopamine-producing brain cells. These cells will be generated from induced pluripotent stem cells -- cells that can give rise to any type of cells in the human body -- donated by people with PD. Alpha-synuclein in these cells will be specifically labeled to facilitate the study of protein clumping. We will use sophisticated research methods to describe the fine structure and size of alpha-synuclein clumps.

Impact on Diagnosis/Treatment of Parkinson's disease; next Steps for Development:
Our project has the potential to explain the mechanisms of protein clumping and to identify robust targets for the development of efficacious therapeutic strategies for the prevention of alpha-synuclein clumping. Our findings will potentially open new avenues for personalized medicine.


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