MYT1L promotes autophagy to ameliorate amyloid-β pathology and cognitive deficits in Alzheimer's disease via Notch signaling pathway.

Autophagy is essential in the growth and advancement of Alzheimer's disease (AD). Myelin transcription factor 1-like (MYT1L) has been reported to have neuroprotective properties; however, its precise role in AD is still unclear. This study identified a reduction in MYT1L expression in the hippocampal neurons of AD model mice. Interestingly, increasing MYT1L expression in these neurons helped alleviate cognitive impairments in APP/PS1 mice. Additionally, MYT1L overexpression reduced the amyloid-beta (Aβ) burden, promoted autophagy, and provided neuroprotection in the hippocampus of these mice. Further investigation of the mechanisms revealed that MYT1L overexpression downregulated the Notch signaling pathway in Aβ25-35-induced SH-SY5Y cells, which in turn promoted autophagy and protected neuronal health. These results highlight previously unrecognized roles of MYT1L in neuronal protection, suggesting that MYT1L could be an intriguing therapeutic target for AD.