Molecular pathway shared by two neurodegenerative disorders found
2022
National Institutes of Health (NIH), Bethesda, USA(1)
UCL Queen Square Institute of Neurology, London, United Kingdom(2)
UCL Queen Square Institute of Neurology, London, United Kingdom(2)
This study elucidates how the mislocalization of the TDP-43 protein alters the genetic instructions for UNC13A. Amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) are two neurodegenerative disorders often characterized by mislocalization of the TDP-43 protein, where instead of being primarily located in the nucleus of the cell, it forms aggregates outside the nucleus. Using human iPSC-derived neurons, as well as postmortem human brain and spinal cord tissue, the study demonstrates a genetic link between the loss of nuclear TDP-43 function and disease. It also reveals the mechanism by which UNC13A variants exacerbate the effects of decreased TDP-43 function. According to the researchers, this discovery could provide a possible therapeutic target for ALS, FTD and other forms of dementia.
TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A
Michael E. Ward(1), Pietro Fratta(2)
Added on: 03-16-2022
[1] https://www.nature.com/articles/s41586-022-04436-3[2] https://www.drugtargetreview.com/news/101753/molecular-pathway-shared-by-two-neurodegenerative-disorders-found/?utm_source=Email+marketing&utm_medium=email&utm_campaign=DTR+-+Newsletter+10+-+Metabolon+-+10.03.2022&utm_term=New+research+points+to+a+possible+driver+of+Parkinson%e2%80%99s+disease&utm_content=https%3a%2f%2femails.drugtargetreview.com%2frussellpublishinglz%2f&gator_td=J24ZhBLGlwEXmVsQoB7n%2bORde09bKvizqWDTCLsx4SlCSQ%2f9JeqgvLaHIwzIvMWl2QRttRzJPQxuqgMjmPxhA5kAJ%2bevp04WhZ%2bfp3w0pJlc%2bsocCqGUijGPvu%2f8rfZZbaX4CZVrfZF491G7OQ34f7AWENex6CBfzlp%2f5n7coYbPMb%2fwb73nGXoqWINv6o8sryD8q%2fZ82Bw6LtlJ57otWmdCz1dAh9NMnC1ynZ%2b2h%2bE%3d
