Alpha-synuclein as a Major Regulator of Iron Homeostasis

Objective/Rationale:

Alpha-synuclein is a key protein involved in Parkinson’s disease. Attempts have been made with drugs to lower the amount of this protein in the brain as a potential treatment for Parkinson’s disease. However, neither the normal function of this protein nor the consequences of its reduction (e.g. by drugs) are well understood. We aim to investigate pre-clinical models with no alpha-synuclein and models with half the amount of alpha synuclein to determine if they develop adverse symptoms.

Project Description:

We have evidence that the essential element, iron, is altered in pre-clinical models lacking the alpha-synuclein protein. This is associated with several adverse outcomes including motor impairment and brain cell loss. We suspect that these adverse consequences emerge as the model ages. We will comprehensively characterize the effect of removing alpha-synuclein on the iron status of the models, and other indicators of health. We will also characterize models that have half the normal amount of alpha-synuclein to determine if a partial lowering of alpha-synuclein is also associated with adverse health outcomes.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:

Many potential therapeutic strategies have been devised to lower the amount of alpha-synuclein with the body of patients with Parkinson’s disease. This project will investigate whether lowering alpha-synuclein could be dangerous to one’s essential iron metabolism.

Anticipated Outcome:

This project will inform us whether lowering alpha-synuclein is a safe approach as a therapeutic strategy for Parkinson’s disease. We expect to discover a functional role for alpha-synuclein in regulating normal iron levels within the body. Such information will be useful for conducting the safety appraisal of new candidate drugs that lower alpha-synuclein levels.

Research Institution

Florey Institute for Neuroscience and Mental Health

Associate Professor David Finkelstein shares further information on this project in Layman’s terms