Affiliations: [a] Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada | [b] Krembil Research Institute, Toronto, ON, Canada
| [c] Department of Chemistry, University of Toronto, Toronto, ON, Canada
| [d] Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada
Correspondence:
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Correspondence to: Mark A. Reed, DPhil, Krembil Discovery Tower, 4th Floor, 4KD-474, 60 Leonard Avenue, Toronto, ON M5T 0S8, Canada. Tel.: +1 416 603 5800 ext. 7352; E-mail: mark.reed@uhnresearch.ca.
Abstract: Alzheimer’s disease (AD) is the most common form of dementia. Although AD is one of the most socioeconomically devastating diseases confronting humanity, no “curative” disease modifying drug has been identified. Recent decades have witnessed repeated failures of drug trials and have called into question the utility of the amyloid hypothesis approach to AD therapeutics design. Accordingly, new neurochemical processes are being evaluated and explored as sources of alternative druggable targets. Among these newly identified targets, neuroinflammation is emerging as a front-runner, and within the realm of neuroinflammation, the inflammasome, particularly the NLRP3 complex, is garnering focussed attention. This review summarizes current data and approaches to understanding the role of the NLRP3 inflammasome in neuroinflammation and AD, and systematically identifies and evaluates multiple targets within the NLRP3 inflammasome cascade as putative drug targets.
