华体汇综合:神经科学研究中心 The Neuroscience Research Center
Combination of traditional Chinese and western Medicine to prevent and treat neurodegenerative diseases
Disorders of oxidative metabolism, increased production of oxygen free radicals, and immune/inflammatory reactions are critical pathophysiological processes of neuronal death caused by disturbances of oxidative metabolism, endoplasmic reticulum stress, accumulation of unfolded and misfolded proteins are involved in the nerves caused by disturbances of oxidative metabolism—the primary cellular mechanism of meta-death. Disorders of oxidative metabolism participate in the splicing process of metabotropic glutamate receptor mRNA by regulating RNA editing, thereby changing the calcium permeability of neuronal metabotropic glutamate receptors, causing cellular calcium regulation dysfunction and leading to neuronal death. Traditional Chinese Medicine has a wide range of activities in terms of anti-oxidation, anti-free radical and anti-inflammatory. In Traditional Chinese Medicine, small biologically active molecules and traditional Chinese medicine compounds that delay the development of senile neurodegenerative diseases can be found to prevent and treat neurodegenerative diseases, mainly Alzheimer's disease.
Research on the molecular regulation mechanism of crucial targets in neurodegenerative diseases
In the Traditional Chinese Medicine Baogongteng, the natural cholinergic drug Baogongteng-A with tropane scaffold was found. Traditionally, natural tropane compounds, such as atropine, have anticholinergic activities. Using Baogongteng-A as a lead, a series of derivatives could be designed, synthesized and evaluated. By using molecular docking, quantitative structure-activity relationship, molecular dynamics simulation, the structure-activity relationship of tropane scaffold could be elucidated. With crystal structures, the structural, pharmacological mechanism of the tropane scaffold activity would be clarified.
Target discovery based on surface plasmon resonance analysis and proximity labelling technology.
Among many natural products, some showed exact bioactivities at the cellular level or even in animals, but the targets are largely unknown. Finding specific targets is a difficult task of natural medicine research. SPR technology combined with MS can enrich the target protein from specific cells or tissues and analyze the sequence and abundance information of the target protein. This method has the characteristics of real-time visibility and high specificity. Proximity labelling technology can further efficiently screen out the relevant proteins for signal transduction downstream of the target, which is essential for elucidating the mechanism of natural products.