Protein Quality Control Systems and ER Stress as Key Players in SARS-CoV-2-Induced Neurodegeneration

Author:

Gavilán Elena12ORCID,Medina-Guzman Rafael1ORCID,Bahatyrevich-Kharitonik Bazhena12ORCID,Ruano Diego12

Affiliation:

1. Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla (US), 41012 Sevilla, Spain

2. Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Junta de Andalucía, CSIC, University of Seville (US), 41013 Sevilla, Spain

Abstract

The COVID-19 pandemic has brought to the forefront the intricate relationship between SARS-CoV-2 and its impact on neurological complications, including potential links to neurodegenerative processes, characterized by a dysfunction of the protein quality control systems and ER stress. This review article explores the role of protein quality control systems, such as the Unfolded Protein Response (UPR), the Endoplasmic Reticulum-Associated Degradation (ERAD), the Ubiquitin–Proteasome System (UPS), autophagy and the molecular chaperones, in SARS-CoV-2 infection. Our hypothesis suggests that SARS-CoV-2 produces ER stress and exploits the protein quality control systems, leading to a disruption in proteostasis that cannot be solved by the host cell. This disruption culminates in cell death and may represent a link between SARS-CoV-2 and neurodegeneration.

Funder

Spanish Ministerio de Universidades/NextGenerationEU/Ayudas para la Recualificación del Sistema Universitario Español

Publisher

MDPI AG

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