Literature DB >> 35987974

Scrutinizing the Therapeutic Potential of PROTACs in the Management of Alzheimer's Disease.

Shiveena Bhatia1, Manjinder Singh2, Tanveer Singh3, Varinder Singh4.   

Abstract

Finding an effective cure for Alzheimer's disease has eluded scientists despite intense research. The disease is a cause of suffering for millions of people worldwide and is characterized by dementia accompanied by cognitive and motor deficits, ultimately culminating in the death of the patient. The course of the disease progression has various underlying contributing pathways, with the first and foremost factor being the development and accumulation of aberrant and misfolded proteins exhibiting neurotoxic functions. The impairment of cellular clearance mechanisms adds to their accumulation, resulting in neuronal death. This is where the PROteolysis TArgeting Chimera (PROTAC) technology comes into play, bringing the UPS degradation machinery in the proximity of the target protein for initiating its degradation and clearing abnormal protein debris with unparalleled precision demonstrating an edge over traditional protein inhibitors in many respects. The technology is widely explored in cancer research and utilized in the treatment of various tumors and malignancies, and is now being applied in treating AD. This review explores the application of PROTAC technology in developing lead compounds for managing this deadly disease along with detailing the pieces of evidence justifying its utility and efficacy.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Entities:  

Keywords:  Alzheimer’s disease; Dementia; Neurodegenerative disorders; PROTACs; Protein degradation; UPS machinery

Year:  2022        PMID: 35987974     DOI: 10.1007/s11064-022-03722-w

Source DB:  PubMed          Journal:  Neurochem Res        ISSN: 0364-3190            Impact factor:   4.414


  87 in total

1.  Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system.

Authors:  Claudia G Almeida; Reisuke H Takahashi; Gunnar K Gouras
Journal:  J Neurosci       Date:  2006-04-19       Impact factor: 6.167

Review 2.  Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing.

Authors:  Barry Boland; Wai Haung Yu; Olga Corti; Bertrand Mollereau; Alexandre Henriques; Erwan Bezard; Greg M Pastores; David C Rubinsztein; Ralph A Nixon; Michael R Duchen; Giovanna R Mallucci; Guido Kroemer; Beth Levine; Eeva-Liisa Eskelinen; Fanny Mochel; Michael Spedding; Caroline Louis; Olivier R Martin; Mark J Millan
Journal:  Nat Rev Drug Discov       Date:  2018-08-17       Impact factor: 84.694

Review 3.  The role of ubiquitin proteasomal system and autophagy-lysosome pathway in Alzheimer's disease.

Authors:  Yuan Zhang; Xu Chen; Yanfang Zhao; Murugavel Ponnusamy; Ying Liu
Journal:  Rev Neurosci       Date:  2017-11-27       Impact factor: 4.353

Review 4.  Prion-like transmission of protein aggregates in neurodegenerative diseases.

Authors:  Patrik Brundin; Ronald Melki; Ron Kopito
Journal:  Nat Rev Mol Cell Biol       Date:  2010-04       Impact factor: 94.444

Review 5.  Protein degradation-associated mechanisms that are affected in Alzheimer´s disease.

Authors:  Angeles C Tecalco-Cruz; José Pedraza-Chaverri; Alfredo Briones-Herrera; Eduardo Cruz-Ramos; Lilia López-Canovas; Jesús Zepeda-Cervantes
Journal:  Mol Cell Biochem       Date:  2022-01-27       Impact factor: 3.396

Review 6.  Molecular Insight into the Crosstalk of UPS Components and Alzheimer's Disease.

Authors:  Abdullah Al Mamun; Md Mosiqur Rahman; Sonia Zaman; Mst Shirajum Munira; Md Sahab Uddin; Abdur Rauf; Naheed Banu; Ghulam Md Ashraf
Journal:  Curr Protein Pept Sci       Date:  2020       Impact factor: 3.272

Review 7.  Proteinopathy, oxidative stress and mitochondrial dysfunction: cross talk in Alzheimer's disease and Parkinson's disease.

Authors:  Gargi Ganguly; Sasanka Chakrabarti; Uttara Chatterjee; Luciano Saso
Journal:  Drug Des Devel Ther       Date:  2017-03-16       Impact factor: 4.162

8.  Proteinopathy-induced neuronal senescence: a hypothesis for brain failure in Alzheimer's and other neurodegenerative diseases.

Authors:  Todd E Golde; Victor M Miller
Journal:  Alzheimers Res Ther       Date:  2009-10-12       Impact factor: 6.982

Review 9.  The ubiquitin-proteasome system in Alzheimer's disease.

Authors:  Salvatore Oddo
Journal:  J Cell Mol Med       Date:  2008-02-08       Impact factor: 5.310

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