Elucidating the consequences of aberrant mGluR1 signalling in cerebellar ataxia

点击翻译按钮获取中文摘要

Ataxia comes from the Greek word 'a taxis' meaning 'lack of order'. Patients suffering from ataxia have problems with their movement, balance and speech, and sometimes develop cognitive disabilities. We study a subgroup of cerebellar ataxias, termed 'spinocerebellar ataxias' (SCAs). These are brain disorders that are caused by the malfunctioning and death of specific nerve cells in the cerebellum, a part of the nervous system that controls movement and coordination. There is currently no cure for SCAs. SCAs are inherited diseases, which means that they are caused by faulty genes, which are passed down through families. Many different genes can cause SCAs, and this presents a great challenge to our understanding of these disorders and, importantly, to efforts in developing potential treatments. Our work focuses on one specific pathway (mGluR1-TRPC3) that regulates the calcium balance within nerve cells and that is commonly disturbed in SCAs. Thus, this pathway provides an exciting novel therapeutic target for SCAs, which we will explore further with the proposed research. Our findings will provide important insights into molecular and cellular processes that go awry in the cerebellum when the mGluR1-TRPC3 pathways is abnormally active. We will study the novel mutations in mGluR1 that we have identified in SCA patients in cell lines, cerebellar nerve cells and a new mouse model. This will shed light on the mechanisms of how these mutations cause disease. We will then use the assays that we have established to identify readily-available and safe drugs that could be used for treatment of SCAs.