Journal
PHARMACOLOGICAL RESEARCH
Volume 184, Issue -, Pages -Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2022.106404
Keywords
Alzheimer's disease; Microglia; Synaptic plasticity; Neuroprotection; Neuroinflammation; Drug discovery
Categories
Ask authors/readers for more resources
This review discusses the pathophysiological roles of microglia in Alzheimer's disease and explores potential pharmacological intervention targets. It also provides evidence for microglia-targeted strategies in preclinical research and early clinical trials.
Numerous clinical trials of anti-amyloid agents for Alzheimer's disease (AD) were so far unsuccessful thereby challenging the validity of the amyloid hypothesis. This lack of progress has encouraged researchers to investigate alternative mechanisms in non-neuronal cells, among which microglia represent nowadays an attractive target. Microglia play a key role in the developing brain and contribute to synaptic remodeling in the mature brain. On the other hand, the intimate relationship between microglia and synapses led to the so-called synaptic stripping hypothesis, a process in which microglia selectively remove synapses from injured neurons. Synaptic stripping, along with the induction of a microglia-mediated chronic neuroinflammatory environment, promote the progressive synaptic degeneration in AD. Therefore, targeting microglia may pave the way for a new disease modifying approach. This review provides an overview of the pathophysiological roles of the microglia cells in AD and describes putative targets for pharmacological intervention. It also provides evidence for microglia-targeted strategies in preclinical AD studies and in early clinical trials.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available