Monophosphoryl lipid A is an lipopolysaccharide-derived Toll-like receptor 4 agonist which may improve Alzheimer's disease pathology.
BACKGROUND
Alzheimer's disease (AD) is partly characterized by the formation of plaques composed of β-amyloid (Aβ) as a result of excessive accumulation of Aβ. Monophosphoryl lipid A (MPL) is a Toll-like receptor 4 agonist commonly used as a nontoxic, FDA-approved adjuvant in viral vaccines.


METHODS
Previous reports had shown MPL as an effective adjuvant for Aβ vaccinations to decrease Aβ deposition. Recently, it was discovered that MPL monotherapy in APP/PS1 transgenic AD mice had beneficial effects, such as decreasing the number and size of deposits, decreasing soluble Aβ monomers and improving cognition through phagocytic activation of microglia. Unlike the parental endotoxin lipopolysaccharide (LPS), MPL stimulated microglial phagocytosis of Aβ, while only minimally increasing a proinflammatory response.


CONCLUSIONS
MPL is a promising therapeutic option for AD treatment due to its ability to promote Aβ clearance without eliciting a strong adverse inflammatory response. Since MPL is already FDA-approved in humans, clinical application can be accelerated. Further analysis of how MPL affects other hallmarks of AD pathology such as dystrophic neurites and hyperphosphorylated tau aggregates, as well as its mechanism of action, will facilitate the understanding of the therapeutic benefits that MPL can produce.
University of Washington, Department of Neurological Surgery , 1959 NE Pacific St, Seattle, WA 98195 , USA +1 206 543 9763 ; +1 206 543 8315 ; dbwang@u.washington.edu.
David B
DB
Wang
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000473:pathology* / Q000517:prevention & control*; D000818:Animals; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D051197:Toll-Like Receptor 4 / Q000819:agonists*
D000276:Adjuvants, Immunologic; D008050:Lipid A; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; C048436:monophosphoryl lipid A