A novel cyclic peptide (Naturido) modulates glia-neuron interactions in vitro and reverses ageing-related deficits in senescence-accelerated mice

The use of agents that target both glia and neurons may represent a new strategy for the treatment of ageing disorders. Here, we confirmed the presence of the novel cyclic peptide Naturido that originates from a medicinal fungus (Isaria japonica) grown on domestic silkworm (Bombyx mon). We found that Naturido significantly enhanced astrocyte proliferation and activated the single copy gene encoding the neuropeptide VGFand the neuron-derived NGFgene. The addition of the peptide to the culture medium of primary hippocampal neurons increased dendrite length, dendrite number and axon length. Furthermore, the addition of the peptide to primary microglial cultures shifted CGA-activated microglia towards antiinflammatory and neuroprotective phenotypes. These findings of in vitro glia-neuron interactions led us to evaluate the effects of oral administration of the peptide on brain function and hair ageing in senescence-accelerated mice (SAMP8). In vivo analyses revealed that spatial learning ability and hair quality were improved in Naturido-treated mice compared with untreated mice, to the same level observed in the normal ageing control (SAMR1). These data suggest that Naturido may be a promising glia-neuron modulator for the treatment of not only senescence, but also Alzheimer's disease and other neurodegenerative diseases.

Automated summary

The study confirmed the significant effects of the novel cyclic peptide Naturido from medicinal fungus on both glia and neurons, promoting astrocyte proliferation, activating specific genes, and increasing dendrite length in neurons. Moreover, Naturido was found to shift microglial activation towards anti-inflammatory and neuroprotective phenotypes, leading to improved brain function and hair quality in senescence-accelerated mice. These results suggest that Naturido may be a promising modulator for the treatment of senescence, Alzheimer's disease, and other neurodegenerative diseases.