RESUMEN
Collapse response mediator proteins (CRMPs) are a family of cytoplasmic phosphorylated proteins, and the mechanism of action has always been the research focus of neurological diseases. Previous studies on the CRMPs family have revealed that CRMPs mediate the growth and development of neuronal cytoskeleton through different signaling pathways in the body. It plays an important role in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and spinocerebellar ataxia, which has attracted the attention of researchers. This article reviews the recent literature on the biological characteristics and mechanisms of CRMPs in different neurodegenerative diseases.
Asunto(s)
Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/metabolismo , Neuronas/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
BRCA1-BRCA2-containing complex subunit 3 (BRCC3), a Lys-63-specific deubiquitinase, is a member of the JAMM/MPN family of zinc metalloproteases. BRCC3 have been shown to promote the inflammasome activation by deubiquitinating NOD-like receptor containing pyrin domain 3 (NLRP3). We reported the involvement of neuronal inflammasome in Parkinson's Disease (PD), but the molecular mechanism remains unknown. In this study, we showed that BRCC3 expression was increased in PD models. Knock-down of BRCC3 with shRNA lentivirus decreased NLRP3 neuronal inflammasome. Interestingly, upregulating cyclin-dependent kinase 5 (Cdk5) increased the expression of BRCC3 in HEK293 cell, while inhibition of Cdk5 decreased the upregulated BRCC3 level in MPP+-induced PD cell model. The interaction between Cdk5 and BRCC3 was further confirmed by immunoprecipitation. Moreover, inhibition of Cdk5 suppressed the expression of NLRP3, pro-caspase-1, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) and interleukin-1 beta (IL-1ß). Besides, inhibition of BRCC3 blocked the increased secretion of IL-1ß. Together, these results suggest that Cdk5-mediated BRCC3 expression may play a critical role in neuronal inflammation by regulating the NLRP3 inflammasome in PD.