Biophysics reveals that autophagy genes participate in the regulation of learning and memory functions

  Through the method of screening nematode genes, early research by Zhang Hong's research team at the Institute of Biophysics of the Chinese Academy of Sciences found that the epg-6 gene is an important autophagy gene unique to multicellular organisms. The homologue of the epg-6 gene in mammals is WDR45/WIPI4, and WDR45 encodes a PtdIn(3)P binding protein containing the WD40 repeat sequence. Human genetic studies have found that mutations in the WDR45 gene can cause a neurodegenerative disease-BPAN, a neurodegenerative disease related to β-helix protein. This is NBIA (a neurodegenerative disease involving iron accumulation). In order to study the function of WDR45 gene in mammals, Zhang Hong's research team constructed nervous system-specific Wdr45 gene knockout mice (Nes-Wdr45fl/Y mice).

  Wdr45 gene knockout mice impaired motor coordination and severely impaired learning and memory. Histopathological and immunohistochemical studies have shown that severe axon edema in the brain of Wdr45 knockout mice is related to the accumulation of eosinophils, inhibits the autophagy pathway, and causes autophagy in neurons and edema axons. Known to happen.

  The phagocytic substrate SQSTM1 and ubiquitin accumulate significantly. In conclusion, the phenotype of Wdr45 gene mice (Nes-Wdr45fl/Y mice) is similar to that of BPAN patients, including cognitive impairment and axon homeostasis imbalance. Therefore, this study will help us better understand the etiology of BPAN and further study the role of autophagy in maintaining axon homeostasis.