Alzheimer's disease (AD) is an age-related neurodegenerative disease with amyloid-β (Aβ) deposition as the main pathological feature. It's an important challenge to find new ways to clear Aβ from Brain. The soluble amyloid precursor protein α (sAPPα) is a neuroprotective protein and can attenuate neuronal damage, including toxic Aβ. However, the regulatory role of sAPPα in non-neuronal cells, such as microglia, is less reported and controversial. Here, we showed that sAPPα promoted the phagocytosis and degradation of Aβ in both normal and damaged microglia. Moreover, the function of damaged microglia was improved by the sAPPα through normalizing mitochondrial function. Furthermore, the results of molecular docking simulation showed that sAPPα had a good affinity with Aβ. We preliminarily reveal that sAPPα is similar to antibodies and can participate in the regulation of microglia phagocytosis and degradation of Aβ after binding to Aβ. sAPPα is expected to be a mild and safe peptide drug or drug carrier for AD.
Keywords: Alzheimer's disease; Drug delivery; biomaterials; mitochondrion; sAPPα peptide.
© 2024 Wiley‐VCH GmbH.