Effects of heparan sulfate from porcine mucosa on Aβ1-42-induced neurotoxicity in vitro and in vivo

Amyloid-beta (A beta) deposition and neurotoxicity play an important role in Alzheimer's disease (AD). Notably, the nonnegligible role of endogenous heparan sulfate (HS) in the release, uptake and misfolding of A beta sheds light on the discovery of HS as an effective drug for AD. In this work, the effects of HS from porcine mucosa (PMHS) on A beta(1-42)-induced neurotoxicity were investigated both in vitro and in vivo. The in vitro AD model was established in SH-SY5Y via treatment with oligomeric A beta(1-42), and the in vivo AD model was established by intracerebroventricular injection of A beta(1-42) to KM mice. The results showed that in vitro, PMHS could ameliorate the inflammation and apoptosis response of SH-SY5Y cells induced by A beta(1-42); in vivo, PMHS could not only improve the cognitive impairment induced by A beta(1-42) but also inhibit neuroinflammation and apoptosis in the brain. Furthermore, PMHS lowered the levels of A beta(1-42) in the peripheral circulation and brain by improving the phagocytosis function of neutrophils. This is the first report that PMHS enhances the phagocytosis function of neutrophils to alleviate A beta-induced neurotoxicity. Moreover, our work verified the feasibility of peripheral A beta clearance for improving neurotoxicity. Conclusively, we believe that PMHS could be developed into neuroprotective drugs for AD.