Parkinson’s disease is a debilitating disorder characterised by movement disorders, including tremor, cognitive dysfunction and non-motor impairments. It is the second most common age-related neurodegenerative disease with ~10 million sufferers worldwide, but the causes of tremor are poorly understood and treatment is wholly inadequate. This project will use a multidisciplinary approach which marries the expertise of research scientists and clinicians in hospitals, universities and Institutes of Technology to examine how LINGO1 levels in the human brain are associated with tremor in Parkinson’s. We will aim to identify the cells in which LINGO1 is upregulated, unravel the complex interplay between LINGO1 and ion channels, and detail the precise molecular interactions that lead to the functional knockdown of BK channels by LINGO1. The main impact that this project will have is to enable a pharmacological targeting of LINGO1 for the treatment of Parkinson’s disease and other conditions such as Essential Tremor. Our research will take important steps towards achieving this goal: We will investigate key biological mechanisms involved in LINGO1’s mechanism of action and BK channel regulation, test first candidates targeting LINGO1, and develop novel pre-clinical models in which drugs targeting LINGO1 can be tested by academic and industrial partners in the future.
Principal Investigator/Researchers: Jochen Prehn