High ‐density lipoprotein mimetic peptide 4F mitigates amyloid‐β‐induced inhibition of apolipoprotein E secretion and lipidation in primary astrocytes and microglia

This study was designed to investigate the impact of an HDL mimetic peptide, 4F, on the secretion and lipidation of apoE. We found that 4F significantly increases apoE secretion and lipidation in primary human astrocytes as well as in pri mary mouse astrocytes and microglia. Aggregated Aβ inhibits glial apoE secretion and lipidation, causing accumulation of intracellular apoE, an effect that is counteracted by co‐treatment with 4F. Pharmacological and gene editing approaches show that 4F mediates its effects partially through the secretory pathway from the endoplasmic reticulum to the Golgi apparatus and requires the lipid transporter ATP‐binding cassette transporter A1. We conclude that the HDL mimetic peptide 4F promotes glial apoE secretion and lipidation and mitigates the detrimental effects of Aβ on proper cellular t rafficking and functionality of apoE. These findings suggest that treatment with such an HDL mimetic peptide may provide therapeutic benefit in AD.Read the Editorial Highlight for this article on doi:10.1111/jnc.14554.
Source: Journal of Neurochemistry - Category: Neurology Authors: Tags: Original Article Source Type: research