Projects per year
Abstract
Alzheimer’s disease (AD) is the most common dementia in the elderly and its increasing prevalence presents treatment challenges. Despite a better understanding of the disease, the current mainstay of treatment cannot modify pathogenesis or effectively address the associated cognitive and memory deficits. Emerging evidence suggests adenosine G protein-coupled receptors (GPCRs) are promising therapeutic targets for Alzheimer’s disease. The adenosine A1 and A2A receptors are expressed in the human brain and have a proposed involvement in the pathogenesis of dementia. Targeting these receptors preclinically can mitigate pathogenic β-amyloid and tau neurotoxicity whilst improving cognition and memory. In this review, we provide an accessible summary of the literature on Alzheimer’s disease and the therapeutic potential of A1 and A2A receptors. Although there are no available medicines targeting these receptors approved for treating dementia, we provide insights into some novel strategies, including allosterism and the targeting of oligomers, which may increase drug discovery success and enhance the therapeutic response.
Original language | English |
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Pages (from-to) | 359–381 |
Number of pages | 23 |
Journal | Purinergic Signalling |
Volume | 18 |
DOIs | |
Publication status | Published - Jul 2022 |
Keywords
- Adenosine
- Allosterism
- Alzheimer’s
- Dementia
- GPCR
- Oligomerisation
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Positive allosteric modulation of anti-convulsant G protein-coupled receptor signalling to treat drug-resistant epilepsy
May, L. (Primary Chief Investigator (PCI)), Webb, G. (Chief Investigator (CI)), Carlsson, J. (Chief Investigator (CI)), Baltos, J.-A. (Chief Investigator (CI)), TN Nguyen, A. (Chief Investigator (CI)), Christopoulos, A. (Associate Investigator (AI)), Miao, Y. (Associate Investigator (AI)), O'Brien, T. (Associate Investigator (AI)), Rollo, B. (Associate Investigator (AI)), Casillas-Espinosa, P. (Associate Investigator (AI)), Gregory, K. (Associate Investigator (AI)), Scammells, P. (Associate Investigator (AI)) & Nguyen, T. (Associate Investigator (AI))
1/01/22 → 31/12/25
Project: Research
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ARC Industrial Transformation Training Centre for Cryo-Electron Microscopy of Membrane Proteins for Drug Discovery
Sexton, P. (Primary Chief Investigator (PCI)), Rouiller, I. (Chief Investigator (CI)), Wootten, D. (Chief Investigator (CI)), van Oijen, A. (Chief Investigator (CI)), Parker, M. W. (Chief Investigator (CI)), Lucet, I. (Partner Investigator (PI)), Griffin, M. (Chief Investigator (CI)), Adams, D. J. (Chief Investigator (CI)), Czabotar, P. E. (Partner Investigator (PI)), Flocco, M. (Partner Investigator (PI)), Han, S. (Partner Investigator (PI)), Shepherd, R. (Partner Investigator (PI)), Ciferri, C. (Partner Investigator (PI)), Williams, P. A. (Partner Investigator (PI)), Brown, D. (Partner Investigator (PI)), Schreuder, H. (Partner Investigator (PI)), Reedtz-Runge, S. (Partner Investigator (PI)), Drinkwater, C. (Partner Investigator (PI)), Howard, B. L. (Partner Investigator (PI)), Betigeri, G. (Partner Investigator (PI)), Pryor, E. (Partner Investigator (PI)), How, J. (Project Manager) & Christopoulos, T. (Chief Investigator (CI))
Boehringer Ingelheim (Germany), AstraZeneca (United Kingdom)
23/03/21 → 23/03/27
Project: Research
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Finely tuned glutamate receptor inhibitors as novel therapeutics for neurodegenerative disorders
Gregory, K. (Primary Chief Investigator (PCI)), Bradley, S. J. (Chief Investigator (CI)) & Rook, J. M. (Chief Investigator (CI))
1/01/21 → 31/12/24
Project: Research