The BRCC3 regulated by Cdk5 promotes the activation of neuronal NLRP3 inflammasome in Parkinson's disease models.
Biochem Biophys Res Commun
; 522(3): 647-654, 2020 02 12.
Article
en En
| MEDLINE
| ID: mdl-31787240
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson
/
Quinasa 5 Dependiente de la Ciclina
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Inflamasomas
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Enzimas Desubicuitinizantes
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Neuronas
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2020
Tipo del documento:
Article
País de afiliación:
China