Md. Tanvir Kabir, Md. Sahab Uddin*, Ahmed Abdeen, Ghulam Md Ashraf, Asma Perveen, Abdul Hafeez, May N. Bin-Jumah and Mohamed M. Abdel-Daim Pages 2025 - 2043 ( 19 )
Several proteolytic systems including ubiquitin (Ub)-proteasome system (UPS), chaperonemediated autophagy (CMA), and macroautophagy are used by the mammalian cells to remove misfolded proteins (MPs). UPS mediates degradation of most of the MPs, where Ub-conjugated substrates are deubiquitinated, unfolded, and passed through the proteasome’s narrow chamber, and eventually break into smaller peptides. It has been observed that the substrates that show a specific degradation signal, the KFERQ sequence motif, can be delivered to and go through CMA-mediated degradation in lysosomes. Macroautophagy can help in the degradation of substrates that are prone to aggregation and resistant to both the CMA and UPS. In the aforesaid case, cargoes are separated into autophagosomes before lysosomal hydrolase-mediated degradation. Even though the majority of the aggregated and MPs in the human proteome can be removed via cellular protein quality control (PQC), some mutant and native proteins tend to aggregate into β-sheet-rich oligomers that exhibit resistance to all identified proteolytic processes and can, therefore, grow into extracellular plaques or inclusion bodies. Indeed, the buildup of protease-resistant aggregated and MPs is a usual process underlying various protein misfolding disorders, including neurodegenerative diseases (NDs) for example Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. In this article, we have focused on the contribution of PQC in the degradation of pathogenic proteins in NDs.
Protein misfolding, Ubiquitin-proteasome system, Macroautophagy, Chaperone mediated autophagy, Neurodegeneration, Amyloid β, Tau.
Department of Pharmacy, Brac University, Dhaka, Department of Pharmacy, Southeast University, Dhaka, Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Glocal School of Life Sciences, Glocal University, Saharanpur, Glocal School of Pharmacy, Glocal University, Saharanpur, Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11474, Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522