@article {Joo76, author = {Yuyoung Joo and Hye-Sun Kim and Ran-Sook Woo and Cheol Hyoung Park and Ki-Young Shin and Jean-Pyo Lee and Keun-A Chang and Seonghan Kim and Yoo-Hun Suh}, title = {Mefenamic Acid Shows Neuroprotective Effects and Improves Cognitive Impairment in in Vitro and in Vivo Alzheimer{\textquoteright}s Disease Models}, volume = {69}, number = {1}, pages = {76--84}, year = {2006}, doi = {10.1124/mol.105.015206}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Nonsteroidal anti-inflammatory drugs (NSAIDs) exert anti-inflammatory, analgesic, and antipyretic activities and suppress prostaglandin synthesis by inhibiting cyclooxygenase, an enzyme that catalyzes the formation of prostaglandin precursors from arachidonic acid. Epidemiological observations indicate that the long-term treatment of patients suffering from rheumatoid arthritis with NSAIDs results in reduced risk and delayed onset of Alzheimer{\textquoteright}s disease. In this study, we investigated the therapeutic potential for Alzheimer{\textquoteright}s disease of mefenamic acid, a commonly used NSAID that is a cyclooxygenase-1 and 2 inhibitor with only moderate anti-inflammatory properties. We found that mefenamic acid attenuates the neurotoxicities induced by amyloid β peptide (Aβ)1{\textendash}42 treatment and the expression of a Swedish double mutation (KM595/596NL) of amyloid precursor protein (Swe-APP) or the C-terminal fragments of APP (APP-CTs) in neuronal cells. We also show that mefenamic acid decreases the production of the free radical nitric oxide and reduces cytochrome c release from mitochondria induced by Aβ1{\textendash}42, Swe-APP, or APP-CTs in neuronal cells. In addition, mefenamic acid up-regulates expression of the antiapoptotic protein Bcl-XL. Moreover, our study demonstrates for the first time that mefenamic acid improves learning and memory impairment in an Aβ1{\textendash}42-infused Alzheimer{\textquoteright}s disease rat model. Taking these in vitro and in vivo results together, our study suggests that mefenamic acid could be used as a therapeutic agent in Alzheimer{\textquoteright}s disease.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/69/1/76}, eprint = {https://molpharm.aspetjournals.org/content/69/1/76.full.pdf}, journal = {Molecular Pharmacology} }