Alterations in the morphology of mushroom bodies in VCP/TER94 knockdown flies were rescued by the coexpression of wild-type VCP/TER94, but to a lesser extent by the coexpression of disease-associated mutant VCP/TER94. Credit: Dr. Masaaki Gold
Researchers have uncovered the mechanism underlying frontotemporal lobar degeneration (FTLD) caused by variants in the valosin-containing protein (VCP) gene. Their study, which used a fruit fly model, reveals key insights into the disease, laying the groundwork for future therapeutic development.
The findings are published in Disease Models & Mechanisms. The research groups were led by Associate Professor Masaki Sone from the Faculty of Science, Toho University, and Professor Hitoshi Okazawa from Institute of Science Tokyo and Maastricht University in the Netherlands.
Mechanisms underlying FTLD are caused by variants in the VCP gene. The abnormal proliferation of neural stem cells during neural development, triggered by the loss of VCP gene function, leads to neurodegenerative symptoms.
FTLD is a major cause of dementia, with a prevalence second only to that of Alzheimer’s disease and Lewy body dementia. Mutations in the VCP gene are known to cause hereditary FTLD. Previous collaborative studies, including those by Professor Hitoshi Okazawa’s team at Institute of Science Tokyo and Associate Professor Masaki Sone’s team at Toho University had identified that DNA damage during the fetal stage affects the onset of FTLD after decades of using a mouse model.
In the new work, the team employed a fruit fly model to show that the loss of VCP gene function leads to abnormal proliferation of neural stem cells during the developmental stage. This abnormality has been identified as a direct cause of neurodegenerative symptoms. These findings offer fundamental insights for the development of new treatments for FTLD.
More information:
Kohei Tsumaki et al, Loss of function of VCP/TER94 causes neurodegeneration, Disease Models & Mechanisms (2024). DOI: 10.1242/dmm.050359
Citation: Research elucidates the mechanism behind frontotemporal lobar degeneration (2025, January 21) retrieved 21 January 2025 from
This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.