Project goal: The aim of the project is to explore the potential preventive and therapeutic effects of recently proposed antioxidants of natural and synthetic origin using molecular, histological and cognitive behavioral research methods in vitro and in vivo in the APP/PS1 mouse model of Alzheimer's disease.
Project description: Increasing evidence suggests that oxidative stress and neuro inflammation significantly contribute to the mechanisms of AD. However, therapeutic and preventive options with these targets are currently insufficiently investigated and largely underdeveloped. At the same time, several antioxidants of various origins, from synthetic nanoparticles to natural plant extracts and food compounds, were shown to interfere with key molecular and cellular processes underlying the AD. For example, sialic-acid binding lectins ameliorate AD pathology in the CNS [1]. Rich in phenolic acids and flavonols plant extract of Limonium gmelinii suppressed oxidative stress and pro-inflammatory responses induced by NMDA and TNF-α in human primary neurons and astrocytes [2]. Several new nanoparticles based on the fusion of fullerene or fullerenol with dihydroquercetine, an extract obtained from the Dahurian larch, were shown to exert powerful anti-oxidant effect and inhibit amyloid fibril formation [3]. However, most of these studies have been carried out in vitro and need to be expanded to the established in vivo models. One of the most commonly used AD model is APP/PS1, in which transgenic modification leads to the expression of amyloid precursor protein and presinelin 1 in a mouse brain. This mutation results in the development of hallmarks of AD in mutant mice APP/PS1: the formation of pathological amyloid plaques, cognitive and emotional disturbances [4]. Based on the foregoing, we propose to study potential preventive and therapeutic effects of recently proposed antioxidants of natural and synthetic origins, using molecular, histological, and cognitive readouts in vitro and in the above-mentioned AD mouse model. We will utilize previously established protocols of in vitro assays and of cognitive tests, MDA assay, expression of cytokines and cardiovascular markers (platelet activation) in the brain and periphery as described elsewhere
PI: Sholpan Askarova
Co-PI: Andrey Tsoy, Aliya Kassenova
Co-PI: Andrey Tsoy, Aliya Kassenova
Project partners: First Moscow State Medical University named after Sechenov; Al-Farabi Kazakh National University
Realisation period: 2024-2026
Expected results: The efficacy of new anti-oxidants and flavonoid-containing extract to treat or prevent AD-like pathology will be studied that can lead to the development of new remedies of AD; new data linking neuroinflammation, oxidative stress, microbiome will be obtained in the APP/PS1 mouse model that can be extrapolated to the clinical situation in patients with AD and result in the identificantion of new mechansims of this disorder.