Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer’s disease

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dc.contributor.authorMcKee, Chloe G.
dc.contributor.authorHoffos, Madison
dc.contributor.authorVecchiarelli, Haley A.
dc.contributor.authorTremblay, Marie-Ève
dc.date.accessioned2024-01-25T21:57:08Z
dc.date.available2024-01-25T21:57:08Z
dc.date.copyright2023en_US
dc.date.issued2023
dc.description.abstractAs individuals age, microglia, the resident immune cells of the central nervous system (CNS), become less effective at preserving brain circuits. Increases in microglial inflammatory activity are thought to contribute to age-related declines in cognitive functions and to transitions toward mild cognitive impairment (MCI) and Alzheimer’s disease (AD). As microglia possess receptors for communicating with the CNS environment, pharmacological therapies targeting these pathways hold potential for promoting homeostatic microglial functions within the aging CNS. Preclinical and early phase clinical trials investigating the therapeutic effects of pharmacological agents acting on microglia, including reactive oxygen species, TREM2, fractalkine signaling, the complement cascade, and the NLRP3 inflammasome, are currently underway; however, important questions remain unanswered. Current challenges include target selectivity, as many of the signaling pathways are expressed in other cell types. Furthermore, microglia are a heterogenous cell population with transcriptomic, proteomic, and microscopy studies revealing distinct microglial states, whose activities and abundance shift across the lifespan. For example, homeostatic microglia can transform into pathological states characterized by markers of oxidative stress. Selective pharmacological targeting aimed at limiting transitions to pathological states or promoting homeostatic or protective states, could help to avoid potentially harmful off-target effects on beneficial states or other cell types. In this minireview we cover current microglial pathways of interest for the prevention and treatment of age-related cognitive decline and CNS disorders of aging focusing on MCI and AD. We also discuss the heterogeneity of microglia described in these conditions and how pharmacological agents could target specific microglial states.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipCGM is supported by a Jamie Cassels Undergraduate Research Award (JCURA) from the University of Victoria and a Boehm Family Award for Excellence in Science. HAV is supported by a fellowship from the Canadian Institutes of Health Research (CIHR) and is a Michael Smith Health Research BC Research Trainee. M-ET holds a Canada Research Chair (Tier 2) in Neurobiology of Aging and Cognition.en_US
dc.identifier.citationMcKee, C. G., Hoffos, M., Vecchiarelli, H. A., & Tremblay, M-È. (2023). Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer’s disease. Frontiers in Pharmacology, 14, 1125982. https://doi.org/10.3389/fphar.2023.1125982en_US
dc.identifier.urihttps://doi.org/10.3389/fphar.2023.1125982
dc.identifier.urihttp://hdl.handle.net/1828/15884
dc.language.isoenen_US
dc.publisherFrontiers in Pharmacologyen_US
dc.subjectmicroglia
dc.subjectmicroglial diversity
dc.subjectmild cognitive impairment
dc.subjectAlzheimer's disease
dc.subjectpharmacology
dc.subjectInstitute for Aging and Lifelong Health
dc.subjectCentre for Advanced Materials and Related Technology (CAMTEC)
dc.subject.departmentDivision of Medical Sciences
dc.subject.departmentSchool of Medical Sciences
dc.subject.departmentDepartment of Biology
dc.titleMicroglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer’s diseaseen_US
dc.typeArticleen_US

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