USP19 was linked to TDP-43 aggregation and ER stress in ALS-related models
Original source
Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human, Mouse
Related topics
Researchers identified ubiquitin-specific peptidase-19 (USP19) as a protein that promotes aggregation of TDP-43 fragments, particularly at the endoplasmic reticulum. In cell and mouse models, reducing the gene for USP19 decreased TDP-43 pathology and ER stress and improved some motor and memory-related measures. USP19 levels were also increased in brain tissue from people with frontotemporal lobar degeneration-TDP.
Why this matters
The findings identify USP19 as a possible mechanism connecting TDP-43 aggregation with cellular stress in ALS and frontotemporal lobar degeneration-TDP. However, the evidence is mechanistic and largely based on laboratory and mouse models; it does not currently change treatment for people with ALS or frontotemporal lobar degeneration.
Limitations and context
This was a primary research study using in-vitro experiments, animal models and human brain tissue. The human results were observational, and the treatment-relevant effects were shown through genetic reduction of usp19 in mice, not in people. Whether targeting USP19 is safe or beneficial in patients remains unknown.