King's College London

Published in Developmental Cell, the study, led by Professor Jeremy Carlton, King’s College London, and Professor Adrian Isaacs, UK Dementia Research Institute and UCL, provides insights into how dementia and motor neuron disease may develop and opens up new possibilities for treatment to slow progression of these conditions.

Mutations in risk genes can lead to faulty proteins which can cause neurodegenerative diseases. CHMP2B and ANXA11 are proteins that can carry disease-causing mutations for frontotemporal dementia (FTD) and motor neuron disease, also known as amyotrophic lateral sclerosis (ALS). Exactly what these proteins do in cells, and why faults in these proteins lead to neurodegeneration, remains unknown.

In this study, the researchers used incredibly precise lasers and hole-forming molecules to damage the outer membrane of cells. They showed that ANXA11 and CHMP2B move one after the other to sites of membrane damage. Looking more closely, the team found that disease-causing mutations in both of these proteins affected their ability to move to where the damage occurred. This impaired the cell’s ability to repair damage, and ultimately increased cell death in cells with these mutations.

The researchers showed that ANXA11 and CHMP2B both function in the same membrane repair pathway. This suggests that membrane repair could play an important role in reducing cell death and preventing neurodegeneration in these diseases. Enhancing membrane repair capability could be a viable future treatment strategy.

He continued: "This study advances our understanding of how and why neurodegenerative diseases develop and highlights that enhancing membrane repair could be a promising therapeutic target for future treatments.”