Effects of heparan sulfate from porcine mucosa on Aβ-induced neurotoxicity in vitro and in vivo.

Amyloid-β (Aβ) 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 Aβ 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 Aβ-induced neurotoxicity were investigated both in vitro and in vivo. The in vitro AD model was established in SH-SY5Y via treatment with oligomeric Aβ, and the in vivo AD model was established by intracerebroventricular injection of Aβ to KM mice. The results showed that in vitro, PMHS could ameliorate the inflammation and apoptosis response of SH-SY5Y cells induced by Aβ; in vivo, PMHS could not only improve the cognitive impairment induced by Aβ but also inhibit neuroinflammation and apoptosis in the brain. Furthermore, PMHS lowered the levels of Aβ 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 Aβ-induced neurotoxicity. Moreover, our work verified the feasibility of peripheral Aβ clearance for improving neurotoxicity. Conclusively, we believe that PMHS could be developed into neuroprotective drugs for AD.