A research team, led by Prof Lu Jiahong in the Institute of Chinese Medical Sciences at the University of Macau (UM), and another research team, led by Prof Li Min in the School of Chinese Medicine at Hong Kong Baptist University (HKBU), have revealed the molecular mechanism by which the autophagy-related gene NRBF2 (Nuclear Receptor Binding Factor 2) regulates the maturation of autophagosomes and the pathological protein degradation in Alzheimer's disease, which suggests a potential new therapeutic strategy for treating the disease. The study has been published online by the authoritative international academic journal Autophagy.

Alzheimer's disease, also known as dementia, is a neurodegenerative disease that seriously affects the patient’s cognitive and memory functions. There are more than 3,000 people with Alzheimer's disease in Macao, and there are about 10 million people with Alzheimer's disease in China. One of the main factors that contribute to Alzheimer's disease is the accumulation of amyloid protein (Aβ) in the brain. Previous studies conducted by Prof Lu and his collaborators found that NRBF2 can promote the degradation of the C-terminal fragment of amyloid precursor protein (CTF-β) to reduce the formation of amyloid, and that NRBF2 expression is reduced in specific areas of the brains of patients with Alzheimer's disease, which has been shown to affect the memory and cognitive function of mice. This study has found, for the first time, that NRBF2 promotes the autophagosome maturation process by regulating the activity of the CCZ1-MON1A-RAB7 system, and this process helps accelerate the degradation of the C-terminal fragment of the amyloid precursor protein and reduces the formation of amyloid. This finding suggests a potential therapeutic strategy for treating Alzheimer's disease by targeting autophagosome maturation.

The study was supported by the Ministry of Science and Technology of China and the Science and Technology Development Fund, Macau SAR (File no. 024/2017/AMJ), the National Natural Science Foundation of China (File no. 31871024), and UM’s research fund (File no. MYRG2019-00129-ICMS). UM PhD student Cai Cuizan and HKBU Research Assistant Professor Yang Chuanbin are the co-first authors of the study. Prof Lu is the corresponding author. Prof Li and Yang Chuanbin are the co-corresponding authors. For more information about the study, please visit: https://www.tandfonline.com/doi/full/10.1080/15548627.2020.1760623