TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics
This week we profile a recent publication in Neuron from Dr. Ian Mackenzie (pictured), head of Neuropathology at Vancouver General Hospital and professor of Pathology and Laboratory Medicine at the University of British Columbia
Can you provide a brief overview of your lab’s current research focus?
The general focus of our UBC Frontotemporal Dementia (FTD) research group is to improve diagnosis and advance treatment of FTD via better understanding of the genetics, pathophysiology and natural history. My personal area of interest is the molecular basis of FTD and ALS.
What is the significance of the findings in this publication?
Our recent discovery of TIA1 mutations as a cause of ALS and FTD advance our understanding of the molecular basis of these two related neurodegenerative disorders; specifically, it introduces aberrant stress granule response as a novel pathogenic mechanism.
What are the next steps for this research?
Next steps are 1) confirm the finding and clarify the frequency of the mutation in larger cohorts of ALS and FTD patients from more diverse ethnic backgrounds, 2) determine in greater detail the link between stress granule dysfunction, neurodegeneration and the formation of the signature pathology in these cases (abnormal neuronal accumulation of TDP-43 protein).
This research was supported by:
CIHR, CCNA, ALS Canada, Brain Canada