Bruceine F in Brucea Javanica Regulates Cellular STK3 and CK2A2 Targets to Correct Huntington Protein Misfolding in Mammalian Huntington’s Disease

Abstract

Huntington’s disease is an autosomal dominant disorder characterized by progressive central nervous system degeneration characterized by motor, cognitive, and psychiatric disorders. This disease occurs frequently and is not easy to cure. We set out to investigate the pathogenesis of The Hippo pathway mediated by Brucea javanica in Huntington’s disease (HD) by studying the critical role of Brucea javanica in the pathogenesis of Huntington’s disease (HD) to provide a basis for the study of targeted drugs for this disease. Methods: Western blotting was used to rapidly determine YAP/TAZ activity and the expression level of HSF1 in tissues. YAP/TAZ activity and the expression level of HSF1 in tissues will show us the correct transcription level in the nucleus to measure efficacy. Hypothesis: Bruceine F in Brucea Javanica could effectively act on STK3 and CK2A2 targets to increase nuclear YAP activity and HSF1 expression, thus effectively treating Huntington’s disease. Possible Results: 1: Bruceine F does not act effectively on SYK3 and CK2A2 sites. There were no significant changes in YAP activity in either the nucleus or cytoplasm, as well as in STK3 and CK2A2 for all samples,the expression of HSF1 in tissues also did not change significantly. 2: Bruceine F successfully inhibited STK3, but activated CK2A2, and YAP activity was decreased in the cytoplasm and elevated in the nucleus. , HSF1 expression levels were decreased. 3:Bruceine F activated STK3 but inhibited CK2A2, and YAP activity was elevated in the cytoplasm and decreased in the nucleus. , HSF1 expression levels were elevated. 4: Bruceine F activated STK3 and CK2A2, and YAP activity was elevated in the cytoplasm and decreased in the nucleus. , HSF1 expression levels were reduced. 5:Bruceine F inhibited STK3 and CK2A2, YAP activity was decreased in the cytoplasm and increased in the nucleus, and HSF1 expression levels were increased. 6:Bruceine F activated CK2A2 in knockout STK3 mice, and YAP activity was unchanged in the cytoplasmic nucleus with reduced HSF1 expression. 7: Bruceine F inhibited CK2A2 in knockout STK3 mice, YAP activity was unchanged in the cytoplasmic nucleus, and HSF1 expression levels were elevated. 8: Bruceine F inhibited STK3 in knockout CK2A2 mice, and YAP activity was reduced in the cytoplasm and increased in the nucleus, while HSF1 expression levels remained unchanged. 9: Bruceine F activated STK3 in knockout CK2A2 mice, and YAP activity was increased in the cytoplasm and decreased in the nucleus, while HSF1 expression levels remained unchanged.