P2X7 inhibition ameliorates the Ubiquitin-proteasome system impairment associated with neurological diseases

The Ubiquitin Proteasome System (UPS) is the primary intracellular pathway leading to the degradation of misfolded, disassembled, or damaged proteins (Kaushik & Cuervo 2015). The destruction of a target protein is handled by the 26S proteasome complex following the covalent binding of multiple c...

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Detalles Bibliográficos
Autor: Bianchi, Carolina
Tipo de recurso: tesis doctoral
Fecha de publicación:2022
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/3466
Acceso en línea:https://hdl.handle.net/20.500.14352/3466
Access Level:acceso abierto
Palabra clave:577.1(043.2)
Biochemistry
Bioquímica
Bioquímica (Medicina)
Descripción
Sumario:The Ubiquitin Proteasome System (UPS) is the primary intracellular pathway leading to the degradation of misfolded, disassembled, or damaged proteins (Kaushik & Cuervo 2015). The destruction of a target protein is handled by the 26S proteasome complex following the covalent binding of multiple copies of ubiquitin molecules to a substrate protein via an enzymatic cascade (Hershko and Ciechanover,1998). UPS dysfunction has been linked to several neurological disorders, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, and epilepsy (Stefanis and Keller, 2017; Upadhya et al., 2007, Engel et al., 2017). The impact of the UPS in these diseases may be linked to deficiencies in the clearance of misfolded proteins, which can lead to intracellular protein aggregation, cytotoxicity, and cell death (Leight et al., 1991; Neumann et al., 2006)...