Billy Wai-Lung NG, Ph.D. | The Chinese University of Hong Kong; Kim Hei Man CHOW, Ph.D.; Owen Ho KO, Ph.D.
Competition Sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China
Awardee year: 2022
Aging-related neurodegenerative diseases like Alzheimer’s disease are substantial medical and socioeconomic burdens with no effective disease-modify treatments to date. The pathological hallmarks of neurodegenerative diseases involve the misfolding and toxic aggregation of neuronal proteins, leading to a progressive loss of neuronal function. Autophagy is the normal pathway by which healthy neurons digest and clear such proteins to maintain homeostasis. However, the autophagic ability of neurons decline with age and neurodegeneration accelerates at later stages of life. Therefore, the promotion of neuronal autophagy is an attractive strategy towards the prevention and reversal of ageing-related neurodegeneration.
Herbal extracts from the Ginkgo tree (Ginkgo biloba) is one of the most popular dietary supplements with various neuroprotective effects. One of the terpene trilactone natural products of Ginkgo biloba is thought to be responsible for neuroprotective effects against neurodegeneration. However, its chemical instability precludes its preclinical evaluation. We envision that the direct chemical modification of this natural product can rapidly produce diverse chemical libraries that are chemically stable and biologically active. Our preliminary data demonstrates that such derivatives can effectively promote the clearance of proteinopathy in an Alzheimer’s disease model through upregulation of autophagy. Such an unprecedented chemical library would allow the exploration of previously unknown chemical and biological space for the pharmacological management of ageing-related neurodegenerative diseases.