Lentinan attenuates tau phosphorylation and memory deficits in hTau-overexpressing mice

Lentinan (LNT), a polysaccharide extracted from shiitake mushrooms, has been long used in Asia for improving health. Although LNT injections have been approved for cancer treatment in multiple Asian countries, the potential of LNT in alleviating Alzheimer's disease (AD) pathology and associated cognitive impairments remains poorly understood. Thus, this study aimed to assess the neuroprotective effects of LNT.

In vitro tests were performed in HEK 293/tau cells. Moreover, to simulate AD tau pathology, human full-length tau (hTau) expression was induced using adeno-associated virus serotype 2 (AAV2) in C57/BL6 mice. Intragastric LNT administration for 1 month markedly elevated protein phosphatase 2A (PP2A) activity and decreased tau phosphorylation at Ser202/Thr205 (AT8) in AAV2-hTau infected mice.

LNT significantly enhanced cell viability and PP2A activity while reducing tau phosphorylation in HEK 293/tau cells. Furthermore, behavioral tests demonstrated that LNT mitigated cognitive defects induced through hTau overexpression while significantly increasing the expression of synaptic protein expression such as synaptotagmin and synaptophysin.

Our findings suggest that LNT can prevent AD-like tau hyperphosphorylation by activating PP2A and attenuate AD-like cognitive impairments by restoring synaptic plasticity and synaptogenesis. Therefore, LNT is a potential therapeutic candidate for treating tau-related diseases.