Gamma frequency light flicker regulates amyloid precursor protein trafficking for reducing β-amyloid load in Alzheimer's disease model.

ABSTRACT: Inducing gamma oscillations with non-invasive light flicker has been reported to impact Alzheimer's disease-related pathology. However, it is unclear which signaling pathways are involved in reducing amyloid load. Here, we found that gamma frequency light flicker increased anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing, and then physically interacted with KCC2, a neuron-specific K⁺ -Cl^- cotransporter, suggesting that it is essential to maintain surface GABA_A receptor α1 levels and reduce β-amyloid (Aβ) production. Stimulation with such light flicker limited KCC2 internalization and subsequent degradation via both tyrosine phosphorylation and ubiquitination, leading to an increase in surface-KCC2 levels.

SUBMITTER: Shen Q 

PROVIDER: S-EPMC8920449 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature