PT  - JOURNAL ARTICLE
AU  - Charles H Wallace
AU  - Giovanni Oliveros
AU  - Peter A Serrano
AU  - Patricia Rockwell
AU  - Lei Xie
AU  - Maria Figueiredo-Pereira
TI  - Timapiprant, a prostaglandin D2 receptor antagonist, ameliorates pathology in a rat Alzheimer’s model
AID  - 10.26508/lsa.202201555
DP  - 2022 Dec 01
TA  - Life Science Alliance
PG  - e202201555
VI  - 5
IP  - 12
4099  - https://www.life-science-alliance.org/content/5/12/e202201555.short
4100  - https://www.life-science-alliance.org/content/5/12/e202201555.full
SO  - Life Sci. Alliance2022 Dec 01; 5
AB  - We investigated the relevance of the prostaglandin D2 pathway in Alzheimer’s disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its contribution to Alzheimer’s disease merits attention, given the known impact of the prostaglandin E2 pathway in Alzheimer’s disease. We used the TgF344-AD transgenic rat model because it exhibits age-dependent and progressive Alzheimer’s disease pathology. Prostaglandin D2 levels in hippocampi of TgF344-AD and wild-type littermates were significantly higher than prostaglandin E2. Prostaglandin D2 signals through DP1 and DP2 receptors. Microglial DP1 receptors were more abundant and neuronal DP2 receptors were fewer in TgF344-AD than in wild-type rats. Expression of the major brain prostaglandin D2 synthase (lipocalin-type PGDS) was the highest among 33 genes involved in the prostaglandin D2 and prostaglandin E2 pathways. We treated a subset of rats (wild-type and TgF344-AD males) with timapiprant, a potent highly selective DP2 antagonist in development for allergic inflammation treatment. Timapiprant significantly mitigated Alzheimer’s disease pathology and cognitive deficits in TgF344-AD males. Thus, selective DP2 antagonists have potential as therapeutics to treat Alzheimer’s disease.