A new study may provide insight into why some people may be at increased risk of developing ALS. The report, led by Harvard Medical School’s Junying Yuan in Boston, Massachusetts, found that NEK1 kinase may help regulate RIP1 kinase by blocking its ability to trigger necroptosis (Amin et al., 2018). The results suggest that key changes in NEK1 may make motor neurons more vulnerable to the disease.
The findings build on previous studies from Project MinE, led by University of Massachusetts Medical School’s John Landers and UMC Utrecht’s Jan Veldink in the Netherlands, which found that variants in the NEK1 gene increase the susceptibility of developing ALS (see August 2016 news; Kenna et al., 2016).
The study appeared on June 26 in the Proceedings of the National Academy of Sciences.
RIP1 kinase may contribute to ALS by promoting inflammation and axonal loss (see September 2016 news; Ito et al., 2016). Scientists at Denali Therapeutics in San Francisco, California are therefore developing potential therapies, including DNL747, which block this enzyme in hopes to protect motor neurons against the disease (see February 2017 news).
DNL747 is emerging as a key alternative to GlaxoSmithKline’s GSK2982772, due to its ability, according to Denali Therapeutics, to be delivered to the brain (see Harris et al., 2017).
A phase 1 clinical trial in the Netherlands is ongoing. The “first-in-man” study launched in March 2018. Stay tuned.
To learn more about the emerging role of RIPK1 in neurodegenerative diseases, check out Targeting RIPK1 May Increase Granularity in FTD.
Amin P, Florez M, Najafov A, Pan H, Geng J, Ofengeim D, Dziedzic SA, Wang H, Barrett VJ, Ito Y, LaVoie MJ, Yuan J. Regulation of a distinct activated RIPK1 intermediate bridging complex I and complex II in TNFα-mediated apoptosis. Proc Natl Acad Sci U S A. 2018 Jun 26;115(26):E5944-E5953. [PubMed].
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For people with ALS and their families, learn more about NEK1 by checking out this FAQ.