Speakers

Biography

Dr. Ailin Liu, a professor, has been working for the Institute of Materia Medica, Chinese Academy of Medical Sciences since 1995. She mainly engages in drug discovery against neurodegenerative diseases and anti-infection diseases. Dr. Liu has taken charge of over 20 national projects and participated in multiple national projects. Based on these projects, more than 170 research papers have been published, more than 50 patents have been applied for, and obtained five rewards for scientific and technological achievement.

Abstract

Alzheimer's disease (AD) has become a serious disease that endangers the health of the elderly, and there is currently no ideal treatment drug available. Due to the complex pathogenesis of AD, it is difficult for single-target drugs to achieve ideal therapeutic effects. At the same time, the idea of multi-target and multi-pathway combined action is a new direction for novel drug development for complicated disease AD treatment.

DL0410 (1,1 '- ([1,1' - biphenyl] -4,4 '- diyl) bis (3- (piperidine-1-yl) propane-1-one) dihydrochloride), also known as diphenyl pyridine, is a novel candidate drug with a novel structure and unique action based on computer-aided design, structural optimization, and functional model evaluation. A series of in vivo and in vitro AD-related pharmacological evaluation models were established to systematically evaluate the efficacy and mechanism of action of DL0410.

The studies on the drug targets in vitro showed that DL0410 exerted significant activity on H3R but also displayed activities on AChE and BuChE. The efficacy results of the nematode anti-aging model show that DL0410 can significantly prolong the lifespan of nematodes. The efficacy results on AD animal models, including the SAMP8 mouse model, APP/PS1 transgenic mouse model, D-galactose-induced aging rat model, D-galactose-induced aging mouse model, and scopolamine-induced learning and memory impairment mouse model, showed that DL0410 can significantly improve the learning and memory ability of AD animal models, improve cognitive level, and the therapeutic effect is mostly better than the positive drug donepezil.

The studies on the mechanism of action suggested that DL0410 can exert anti-AD effects by improving blood-brain barrier damage, promoting neuronutrition, reducing neuronal loss, improving mitochondrial function, improving oxidative stress, improving neuroinflammation, and improving synaptic structure and functional plasticity. Therefore, DL0410 is a promising candidate against AD.