Nogo-66 promotes β-amyloid protein secretion via NgR/ROCK-dependent BACE1 activation

The generation of beta-amyloid protein (A beta) is considered a key step in the pathogenesis of Alzheimer's disease (AD) and the regulation of its production is an important therapeutic strategy. It was hypothesized in the present study that Nogo-A may be involved in AD and may regulate the generation of A beta. Nogo-A is known to act as a major inhibitor of neuron regeneration in the adult central nervous system. A recent study indicated that Nogo-A is associated with AD; however, the underlying effect and molecular mechanisms remain largely elusive. In the present study, the potential effects of Nogo-A on AD were investigated. ELISA was used to detect the levels of A beta, enzymatic activity detection kits were used to determine the activity of secretase enzymes in amyloid precursor protein (APP) metabolism, and western blot analysis was used to detect the expression levels of proteins associated with the APP processing and Nogo-A/Nogo-66 receptor (NgR) signaling pathways. The results revealed that Nogo-66, the major inhibitory region of Nogo-A, promoted neuronal A beta secretion by increasing the activity of beta-secretase 1 via the NgR/Rho-associated coiled-coil containing kinases pathway in a dose-dependent manner. The present data suggested that Nogo-A may facilitate the onset and development of AD by promoting A beta secretion, providing information on a potential novel target for AD therapy.

Automated summary

The study suggests that Nogo-A may be involved in Alzheimer's disease by promoting beta-amyloid protein secretion, potentially providing a new target for therapy. Nogo-A is known for its role as an inhibitor of neuron regeneration in the adult central nervous system, and further research is needed to understand its molecular mechanisms in Alzheimer's disease.