Gene discovery indicates motor neuron diseases caused by abnormal lipid processing in cells

Gene discovery indicates motor neuron diseases caused by abnormal lipid processing in cells


A new genetic discovery adds weight to a theory that motor neurone degenerative diseases are caused by abnormal lipid (fat) processing pathways inside brain cells. This theory will help pave the way to new diagnostic approaches and treatments for this group of conditions. The discovery will provide answers for certain families who have previously had no diagnosis.

Motor neurone degenerative diseases (MNDs) are a large family of neurological disorders. Currently, there are no treatments available to prevent onset or progression of the condition. MNDs are caused by changes in one of numerous different genes. Despite the number of genes known to cause MNDs, many patients still remain without a much-needed genetic diagnosis.

A University of Exeter team led by Professor Andrew Crosby and Dr Emma Baple has a long history of research in motor neurone degenerative diseases. The team developed a hypothesis to explain a common cause of MNDs stemming from their discovery of 15 genes responsible for MNDs. The genes they identified are all involved in processing lipids — in particular cholesterol — inside brain cells. in the new hypothesis published in the leading neurology journal Brain, describes the specific lipid pathways that the team believe are important in the development of MNDs.

Now, the team has identified a further new gene — named “TMEM63C” — which causes a degenerative disease that affects the upper motor neurone cells in the nervous system. Also published in Brain, their latest discovery is important as the protein encoded by TMEM63C is located in the region of the cell where the lipid processing pathways they identified operate. This further bolsters the hypothesis that MNDs are caused by abnormal processing of lipids including cholesterol.

Professor Andrew Crosby, at the University of Exeter, said: “We’re extremely excited by this new gene finding, as it is consistent with our hypothesis that the correct maintenance of specific lipid processing pathways is crucial for the way brain cells function, and that abnormalities in these pathways are a common linking theme in motor neurone degenerative diseases. It also enables new diagnoses and answers to be readily provided for families affected by some forms of MND”

MNDs affect the nerve cells that control voluntary muscle activity such as walking, speaking and swallowing. There are many different forms of MNDs which have different clinical features and severity. As the condition progresses, the motor neurone cells become damaged and may eventually die. This leads to the muscles, which rely on those nerve messages, gradually weakening and wasting away.

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