Sorl1 knockout inhibits expression of brain-derived neurotrophic factor: involvement in the development of late-onset Alzheimer's disease.

Sortilin-related receptor 1 () is a critical gene associated with late-onset Alzheimer's disease. SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellular β-amyloid precursor protein. To better understand the underlying mechanisms of in the pathogenesis of late-onset Alzheimer's disease, in this study, we established a mouse model of gene knockout using clustered regularly interspaced short palindromic repeats-associated protein 9 technology. We found that -knockout mice displayed deficits in learning and memory. Furthermore, the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and cortex, and amyloid β-protein deposits were observed in the brains of -knockout mice. , hippocampal neuronal cell synapses from homozygous -knockout mice were impaired. The expression of synaptic proteins, including Drebrin and NR2B, was significantly reduced, and also their colocalization. Additionally, by knocking out the gene in N2a cells, we found that expression of the N-methyl-D-aspartate receptor, NR2B, and cyclic adenosine monophosphate-response element binding protein was also inhibited. These findings suggest that participates in the pathogenesis of late-onset Alzheimer's disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.