LncRNA BDNF-AS as ceRNA regulates the miR-9-5p/BACE1 pathway affecting neurotoxicity in Alzheimer's disease

Introduction: The long non-coding RNA Brain-derived nutritional factor anti-sense RNA (BDNF-AS) is a type of anti-sense RNA that has been proven to play a crucial role in the occurrence and development of certain nervous system disorders. However, the role and molecular mechanism of BDNF-AS in Alzheimer's disease (AD) have not been elucidated yet. Methods: Peripheral blood samples were collected from outpatients with AD as well as from normal elderly individuals in the community, and the expression of BDNF-AS was analysed using quantitative reverse transcription-polymerase chain reaction. An in vitro model was constructed, and the effect of BDNF-AS expression level on the cells was measured using the CCK8 method and flow cytometry. The molecular biological mechanism of BDNF-AS in AD was examined using the luciferase reporter, MS2-RIP, and RNA pulldown assays. Result: We found that the expression of BDNF-AS was elevated in the peripheral blood of patients with AD and that increased BDNF-AS expression may be associated with the cognitive status of such patients. The results confirmed that BDNF-AS could promote neurotoxicity in the in vitro model. Then, we uncovered that BDNF-AS promotes the expression of BACE1 through the competitive binding of miR-9-5p, thereby promoting amyloid deposition. Finally, through the Morris water maze, we found that the high expression of BDNF-AS promoted cognitive impairment in AD mice. Conclusion: The obtained results suggest that BDNF-AS plays a crucial role in the occurrence and development of AD. As a new pathogenic gene of AD, BDNF-AS may be used as a therapeutic target or as a prognostic marker in patients with AD.

Automated summary

This study found that BDNF-AS is upregulated in patients with AD and may be associated with cognitive status. BDNF-AS can promote neurotoxicity by competitively binding to miR-9-5p to promote the expression of BACE1, thereby promoting amyloid deposition. High expression of BDNF-AS aggravates cognitive impairment in AD mice.