Neuroprotective role of alendronate against APP processing and neuroinflammation in mice fed a high fat diet.

Neuroprotective role of alendronate against APP processing and neuroinflammation in mice fed a high fat diet. Brain Res Bull. 2020 May 07;: Authors: Zameer S, Alam M, Hussain S, Vohora D, Ali J, Akhtar M Abstract Obesity and consumption of diet rich in fat are known to contribute to the development of Alzheimer's disease (AD) which is a complex and multifactorial neurodegenerative disease and a leading cause of mortality with unmet medical needs. Hypercholesterolemia was discovered to increase neuropathological changes alongwith cognitive decline in AD mouse models but still the underlying mechanism is elusive. Furthermore, isoprenoids, the crucial products of Mevalonate-pathway produced by the action of farnesyl pyrophosphate synthase (FPPS) enzyme, are also demonstrated to play a key role in AD. Nevertheless, bisphosphonates target this enzyme in order to treat osteoporosis and also found to alleviate dementia in such patients. As per the cited inhibitory action of alendronate, against acetylcholinesterase and cholesterol level, we hypothesized to explore the potential of alendronate against high fat diet (HFD) induced neuropathologies and cognitive disabilities in AD mouse model. Here we noticed that in mice provided with HFD for 14 weeks, spatial memory was compromised as interpreted in different behavioral paradigms. Together with cognitive depletion, there was observed a provoking effect on amyloid precursor protein (APP)-proce...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research