The article explores the intricate relationship between SARS-CoV-2 and neurodegenerative processes, focusing on the role of protein quality control systems and ER stress. It highlights how SARS-CoV-2 induces ER stress and manipulates these systems, leading to proteostasis disruption and potential neurodegeneration. The review covers the following key points: 1. **Protein Quality Control Systems**: The article discusses the Unfolded Protein Response (UPR), Endoplasmic Reticulum-Associated Degradation (ERAD), Ubiquitin-Proteasome System (UPS), autophagy, and molecular chaperones. These systems are essential for maintaining cellular homeostasis by regulating protein folding, degradation, and turnover. 2. **ER Stress and UPR**: SARS-CoV-2 infection triggers ER stress, which activates the UPR. This response aims to mitigate the burden of unfolded proteins but can lead to cell death if prolonged or severe. The article details how the virus manipulates UPR components to facilitate its replication and evade the host's defense mechanisms. 3. **ERAD and UPS**: The article explains how ERAD and UPS are crucial for maintaining proteostasis and degrading misfolded proteins. SARS-CoV-2 can manipulate these pathways to degrade viral components and facilitate its replication. The article also discusses how viruses use these systems to their advantage, such as degrading host proteins and modulating the expression of ERAD/UPS-related proteins. 4. **Autophagy**: Autophagy plays a dual role in viral infections, acting as both a defense mechanism and a target for viral exploitation. The article explores how SARS-CoV-2 can manipulate autophagy to promote its replication and survival, while also highlighting the potential therapeutic strategies that target autophagy to combat the virus. 5. **Therapeutic Strategies**: The article suggests that targeting the manipulation of protein quality control systems by SARS-CoV-2 could be a promising approach to combat the virus and its associated neurodegenerative complications. It reviews potential therapeutic targets, such as UPS inhibitors and E3 ubiquitin ligases, which have shown promise in reducing viral replication and improving patient outcomes. In conclusion, the article provides a comprehensive overview of the complex interplay between SARS-CoV-2 and protein quality control systems, emphasizing the potential for targeted therapies to address the virus's impact on neurodegeneration.The article explores the intricate relationship between SARS-CoV-2 and neurodegenerative processes, focusing on the role of protein quality control systems and ER stress. It highlights how SARS-CoV-2 induces ER stress and manipulates these systems, leading to proteostasis disruption and potential neurodegeneration. The review covers the following key points: 1. **Protein Quality Control Systems**: The article discusses the Unfolded Protein Response (UPR), Endoplasmic Reticulum-Associated Degradation (ERAD), Ubiquitin-Proteasome System (UPS), autophagy, and molecular chaperones. These systems are essential for maintaining cellular homeostasis by regulating protein folding, degradation, and turnover. 2. **ER Stress and UPR**: SARS-CoV-2 infection triggers ER stress, which activates the UPR. This response aims to mitigate the burden of unfolded proteins but can lead to cell death if prolonged or severe. The article details how the virus manipulates UPR components to facilitate its replication and evade the host's defense mechanisms. 3. **ERAD and UPS**: The article explains how ERAD and UPS are crucial for maintaining proteostasis and degrading misfolded proteins. SARS-CoV-2 can manipulate these pathways to degrade viral components and facilitate its replication. The article also discusses how viruses use these systems to their advantage, such as degrading host proteins and modulating the expression of ERAD/UPS-related proteins. 4. **Autophagy**: Autophagy plays a dual role in viral infections, acting as both a defense mechanism and a target for viral exploitation. The article explores how SARS-CoV-2 can manipulate autophagy to promote its replication and survival, while also highlighting the potential therapeutic strategies that target autophagy to combat the virus. 5. **Therapeutic Strategies**: The article suggests that targeting the manipulation of protein quality control systems by SARS-CoV-2 could be a promising approach to combat the virus and its associated neurodegenerative complications. It reviews potential therapeutic targets, such as UPS inhibitors and E3 ubiquitin ligases, which have shown promise in reducing viral replication and improving patient outcomes. In conclusion, the article provides a comprehensive overview of the complex interplay between SARS-CoV-2 and protein quality control systems, emphasizing the potential for targeted therapies to address the virus's impact on neurodegeneration.