title: The ubiquitin proteasomal system: a potential target for the management of Alzheimer's disease.
abstract: The cellular quality control system degrades abnormal or misfolded proteins and consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy and molecular chaperones. Any disturbance in this system causes proteins to accumulate, resulting in neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and prion or polyglutamine diseases. Alzheimer's disease is currently one of the most common age-related neurodegenerative diseases. However, its exact cause and pathogenesis are unknown. Currently approved medications for AD provide symptomatic relief; however, they fail to influence disease progression. Moreover, the components of the cellular quality control system represent an important focus for the development of targeted and potent therapies for managing AD. This review aims to evaluate whether existing evidence supports the hypothesis that UPS impairment causes the early pathogenesis of neurodegenerative disorders. The first part presents basic information about the UPS and its molecular components. The next part explains how the UPS is involved in neurodegenerative disorders. Finally, we emphasize how the UPS influences the management of AD. This review may help in the design of future UPS-related therapies for AD.
authors.affiliation: Laboratory of Neurobiology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Kundlik
authors.initials: K
authors.lastname: Gadhave
authors.affiliation: Institutional Level Biotech hub (IBT hub), Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Nityanand
authors.initials: N
authors.lastname: Bolshette
authors.affiliation: Laboratory of Neurobiology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Ahire
authors.affiliation: Institutional Level Biotech hub (IBT hub), Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Pardeshi
authors.affiliation: Institutional Level Biotech hub (IBT hub), Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Krishan
authors.initials: K
authors.lastname: Thakur
authors.affiliation: Faculty of Medicine, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Trandafir
authors.affiliation: Faculty of Medicine, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Istrate
authors.affiliation: Laboratory of Neurobiology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Sahabuddin
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Laboratory of Neurobiology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.|Institutional Level Biotech hub (IBT hub), Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Gauhati Medical College, Guwahati, Assam, India.
authors.forename: Mangala
authors.initials: M
authors.lastname: Lahkar
authors.affiliation: Faculty of Medicine, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.|Department of Clinical Neurosciences, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.|"RoNeuro" Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania.
authors.forename: Dafin F
authors.initials: DF
authors.lastname: Muresanu
authors.affiliation: Department of Clinical Neurosciences, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Balea
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Alzheimer's disease; amyloid β; chaperones; ubiquitin