Apelin Receptor Homodimerisation Inhibits Hippocampal Neuronal Autophagy via G Protein-Dependent Signalling in...

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Vascular dementia (VD) involves cerebral hypoperfusion and white matter lesions, with unclear mechanisms and limited targeted therapies.
• Apelin receptors (APJ) can homodimerize, generating distinct signals from monomers, and Apelin-13 shows neuroprotective potential in VD models.
• Understanding APJ homodimerization's role in VD pathogenesis is crucial for developing novel treatments.

Purpose of the Study:

• To investigate the impact of Apelin receptor (APJ) homodimerization on autophagy in a rat and cellular oxygen-glucose deprivation/reoxygenation vascular dementia (VD) model.
• To elucidate the signaling pathways involved in APJ homodimer-mediated neuroprotection.
• To explore APJ homodimers as a potential therapeutic target for VD.

Main Methods:

• Establishment of an in vivo rat model and an in vitro cellular model of oxygen-glucose deprivation/reoxygenation-induced vascular dementia (VD).
• Investigation of the role of Apelin receptor (APJ) homodimerization in regulating autophagy.
• Analysis of downstream signaling pathways, including Gαq, Gαi, and PI3K/Akt/mTOR.

Main Results:

• Apelin receptor (APJ) homodimers were found to protect against vascular dementia (VD) by inhibiting autophagy.
• This protective effect was mediated through the Gαq and PI3K/Akt/mTOR pathways, downstream of Gαi signaling.
• The findings were consistent in both in vivo and in vitro experimental models.

Conclusions:

• Apelin receptor (APJ) homodimers play a significant neuroprotective role in vascular dementia (VD) by suppressing autophagy.
• Targeting APJ homodimerization presents a promising therapeutic strategy for chronic cerebral ischemia-reperfusion diseases.
• This study provides a foundation for developing drugs that modulate APJ homodimers for VD treatment.