SLC38A9 Regulation Affects Hippocampal Neuronal Autophagy: A Potential Alzheimer's Therapeutic Approach by Suppressing Alzheimer's Disease-Related Protein Deposition.

AIMS: Impaired autophagy-mediated clearance of Alzheimer's disease (AD)-related proteins is a critical event in AD pathogenesis. SLC38A9, a member of the Solute Carrier 38 family, acts as an arginine sensor and plays an important role in regulating autophagy. Although the activation of autophagy regulated by the SLC38A9 may have a mitigating effect on AD, this aspect still awaits further exploration.

METHODS

APP/PS1 mouse models and HT22 cells treated with amyloid-β 25-35 (Aβ25-35) were transduced with vectors to evaluate the effect of SLC38A9 in AD.

RESULTS

We show that decreasing SLC38A9 could promote the hippocampal neuronal autophagic clearance of AD-related proteins, reduce neuronal apoptosis, and improve cognitive function.

CONCLUSION

Our results demonstrate SLC38A9 is involved in AD-related pathology and its cognitive impairment, and may offer new therapeutic targets to AD.