A gene involved in the processing of lipids in the brain, has been found to be associated with motor neurone diseases (MNDs), a group of hereditary, neurodegenerative conditions.
Published in Brain, teams at the University of Exeter and the University of Cambridge have linked mutations in the gene TMEM63C to MNDs. These debilitating diseases are characterised by the progressive loss of motor functions due to the degeneration of motor neurons. However, the cause remains unknown and a cure elusive, with current treatments only focusing on the symptoms.
'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' said one of the lead authors, Professor Andrew Crosby from the University of Exeter.
Previously, the team at Exeter had discovered 15 genes implicated in MNDs. The researchers found that all of these genes were involved in processing lipids, particularly cholesterol, inside brain cells. Identification of another gene implicated in MHDs, also involved in lipid processing, further emphasises that MNDs may be caused by the abnormal processing of lipids.
The team used genome sequencing techniques to uncover mutations in this gene by investigating three unrelated families with hereditary spastic paraplegia, a type of MND. Further analysis using state of the art microscopy techniques revealed the localisation of the TMEM63C protein between the endoplasmic reticulum and mitochondria, a region crucial to cellular lipid homeostasis. Silencing of this gene in human-derived cells resulted in morphological changes to mitochondria, a condition that is observed in a number of neurodegenerative diseases.
A second lead author, Dr Emma Baple of the University of Exeter commented: 'Understanding precisely how lipid processing is altered in motor neurone degenerative diseases is essential to be able to develop more effective diagnostic tools and treatments for a large group of diseases that have a huge impact on people's lives. Finding this gene is another important step towards these important goals.'
Many of the genes implicated in MNDs are involved in a wide range of cellular processes. This study adds to understanding the complex processes involved in MNDs and the involvement of lipid metabolism in neuron health. Further work from the team will assess the role of TMEM63C in relevant disease models.