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

TL;DR

Reducing SLC38A9 improves autophagy in brain cells, helping clear harmful proteins linked to Alzheimer's and improving memory.

Contribution

This study identifies SLC38A9 as a novel therapeutic target for Alzheimer's by linking its regulation to autophagy and cognitive function.

Findings

Reducing SLC38A9 promotes autophagic clearance of AD-related proteins in hippocampal neurons.

SLC38A9 suppression reduces neuronal apoptosis and improves cognitive function in AD models.

SLC38A9 impairs autophagy, leading to synaptic damage and neuronal loss in Alzheimer's.

Abstract

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.

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.

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

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

This study demonstrates that SLC38A9 contributes to cognitive impairment in Alzheimer's disease (AD). By impairing autophagic activity in hippocampal neurons, SLC38A9 inhibits the clearance of pathological proteins, thereby exacerbating synaptic damage and neuronal loss. Collectively, these findings identify SLC38A9 as a potential therapeutic target for mitigating cognitive decline in AD, via SLC38A9‐mediated autophagic clearance of pathological proteins..

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