“TMEM63C” gene causes a degenerative disease that affects the upper motor neurone cells in the nervous system.

Gene discovery indicates motor neurone 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. 的 discovery will provide answers for certain families who have previously had no diagnosis.

运动神经元退行性疾病(MNDs)是一大类神经系统疾病. Currently, there are no treatments available to prevent onset or progression of the condition. MNDs是由众多不同基因中的一种改变引起的. 尽管已知有很多基因会导致MNDs, 许多患者仍然没有得到急需的基因诊断.

A University of OG视讯 team led by 教授安德鲁·克罗斯比 and 艾玛Baple博士 has a long history of research in motor neurone degenerative diseases. 这个团队 开发了一种假说 to explain a common cause of MNDs stemming from their discovery of 15 genes responsible for MNDs. 的 genes they identified are all involved in processing lipids - in particular cholesterol – inside brain cells. 这项新假说发表在神经病学杂志上 大脑, describes the specific lipid pathways that the team believe are important in the development of MNDs.

现在,研究小组又发现了一个新的基因,命名为"TMEM63C” – which causes a degenerative disease that affects the upper motor neurone cells in the nervous system. 也发表在 大脑,他们的最新发现是重要的,因为蛋白质编码的 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.

教授安德鲁·克罗斯比, 在OG视讯, 他说:“OG视讯对这个新的基因发现感到非常兴奋, 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会影响控制随意肌活动(如行走)的神经细胞, 说话和吞咽. 的re 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.

如果得到证实, the theory could lead to scientists to use patient samples to predict the course and severity of the condition in an individual, 并监测用于治疗这些疾病的潜在新药的效果.

在最新的研究中, the team used cutting-edge genetic sequencing techniques to investigate the genome of three families with individuals affected by hereditary spastic paraplegia – a large group of MNDs in which the motor neurons in the upper part of the spinal cord miscommunicate with muscle fibres, 导致肌肉僵硬等症状, 软弱和浪费. 的se investigations showed that changes in the TMEM63C gene were the cause of the disease. 与以。为首的团队合作 朱利安博士谨慎 at the Medical 研究 Council Mitochondrial Biology Unit at the University of Cambridge, 该团队还进行了研究,以了解更多的功能相关性 TMEM63C 细胞内的蛋白质.

使用最先进的显微镜方法, the Cambridge team’s work showed that a subset of TMEM63C is localised at the interface between two critical cellular organelles, 内质网和线粒体, a region of the cell required for lipid metabolism homeostasis and proposed by the OG视讯 team to be important for the development of MNDs. 除了这个特定的本地化, 路易斯-卡洛斯·塔巴拉·罗德里格斯博士, 博士后. 普瑞斯的实验室也发现了这个 TMEM63C 控制内质网和线粒体的形态, 这可能反映出它在这些细胞器功能调节中的作用, 包括脂质代谢稳态.

朱利安博士谨慎, MRC线粒体生物学小组的成员, 他说:“从线粒体细胞生物学家的角度来看, 的识别 TMEM63C as a new motor neurone degenerative disease gene and its importance to different organelle functions reinforce the idea that the capacity of different cellular compartments to communicate together, 例如通过交换脂质, 是确保细胞内稳态预防疾病的关键吗.”

艾玛Baple博士, OG视讯, said: “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. 找到这个基因是实现这些重要目标的又一步。”

哈尔平信托, 该慈善机构支持在医疗保健领域产生强大而持久影响的项目, 自然保护与环境保护, 部分资助的这项研究. 克莱尔·哈尔平, the charities' co-founder with her husband Les said “哈尔平信托 are extremely proud of the work ongoing in OG视讯, 这项高度合作的国际研究的重要发现. We’re delighted that the Trust has contributed to this work, which forms part of Les’s legacy. 我知道,他也会很高兴的.”

的 HSP Support Group is a UK charity providing help for people diagnosed with Hereditary Spastic Paraplegia (HSP). 亚当•劳伦斯, the Group’s Chair said “Finding a new type of HSP is extremely important as it helps reduce the uncertainty which people with the condition often have on their diagnosis journey. 的 work of the team in OG视讯 investigating HSP and its genetic causes over many years is world-leading and has increased the global understanding of HSP. 的ir work is important providing much needed answers for people with HSP, and developing treatments.”

这项新研究名为“TMEM63C mutations cause mitochondrial morphology defects and underlie hereditary spastic paraplegia,并于 大脑.