Leukotriene D4 induces cognitive impairment through enhancement of CysLT1R-mediated amyloid-β generation in mice

Antidiabetic drugs restore abnormal transport of amyloid-β across the blood–brain barrier and memory impairment in db / db mice

“…This was performed as descried previously (Tang et al, 2013). The Y-maze was constructed of black plastic walls (10 cm high), consisting of three compartments (10 cm × 10 cm) connected with passages (4 cm × 5 cm), with the floor of 3.175 mm stainless steel rods (8 mm apart).…”

Telmisartan Treatment Ameliorates Memory Deficits in Streptozotocin-Induced Diabetic Mice via Attenuating Cerebral Amyloidosis

“…This was carried out as described previously (21). Mice were individually trained in a circular pool (120-cm diameter, 50-cm height) filled to a depth of 30 cm with water maintained at 25°C.…”

Multitargeted Imidazoles: Potential Therapeutic Leads for Alzheimer’s and Other Neurodegenerative Diseases

“…45,50−52 Although there may be multiple reasons for the lack of efficacy in these clinical trials, including issues with the particular candidate compounds used in the studies and/or trials that were conducted in patient populations with disease that was too advanced to respond to this therapeutic approach, or who had dementia that was not due to underlying AD pathology, another possible mechanistic explanation may be that even if substantial COX inhibition is achieved within the AD brain, this may not prevent the detrimental effects of inflammatory LTs. Indeed, different studies have now shown that these 5-LOX products are likely to contribute to Aβ plaque pathology, 8,18,20,21,23 and there is evidence that blocking COX metabolism can lead to shunting of arachidonic acid to the 5-LOX pathway. 53−55 Furthermore, it may be also argued that any potential benefit of lowering Aβ production and plaque pathology alone may be limited if tau pathology persists.…”

“…4−7 Furthermore, our recent work 8 indicates that the binding of cyclooxygenase (COX)- and 5-lipoxygenase (5-LOX)-derived eicosanoids to their cognate receptors in neurons results in increased production of amyloid precursor protein (APP) and Aβ peptides, adding to a body of literature 9−23 implicating inflammatory eicosanoids as key contributing factors to Aβ plaque deposition in AD. Thus, a stabilization of axonal MTs, combined with a concurrent suppression of eicosanoid production, may be considered as a multitargeted therapeutic strategy that could attenuate both tau- and Aβ-mediated neurodegeneration, as well as MT deficiencies 24 and/or neuroinflammation, 25−31 in AD.…”