Mammalian suppressor of tauopathy 2 (MSUT2)

Mammalian suppressor of tauopathy 2 (MSUT2), also known as ZC3H14, is an RNA-binding protein that plays a critical role in the regulation of tau-mediated neurotoxicity. It is the mammalian ortholog of the C. elegans sut-2 gene, which was identified as a genetic suppressor of tau-induced phenotypes. MSUT2 functions by binding to polyadenosine RNA and regulating the length of poly(A) tails, thereby influencing the stability and transport of specific mRNA transcripts. In the context of neurodegenerative diseases, MSUT2 levels are often altered in the brains of patients with Alzheimer's disease, where it appears to promote the aggregation of tau protein. Research indicates that the depletion or knockdown of MSUT2 can significantly reduce tau pathology and neuronal loss, making it a promising therapeutic target for tauopathies. While no clinical-stage drugs currently target MSUT2, it represents a novel approach to treating dementia by modulating the cellular environment that allows tau to become toxic.

Other names

Zinc finger CCCH domain-containing protein 14ZC3H14Suppressor of tauopathy 2SUT2NY-REN-37

Inhibition of MSUT2 reduces the accumulation of pathological tau protein and mitigates tau-mediated neurotoxicity by modulating the polyadenylation and stability of specific mRNAs involved in tau proteostasis.