%0 Journal Article
%T The neuroprotective effects of milk fat globule-EGF factor 8 against oligomeric amyloid ¦Â toxicity
%A Endong Li
%A Mariko Noda
%A Yukiko Doi
%A Bijay Parajuli
%A Jun Kawanokuchi
%A Yoshifumi Sonobe
%A Hideyuki Takeuchi
%A Tetsuya Mizuno
%A Akio Suzumura
%J Journal of Neuroinflammation
%D 2012
%I BioMed Central
%R 10.1186/1742-2094-9-148
%X The release of MFG-E8 from microglia treated with conditioned medium from neurons exposed to neurotoxic substances, glutamate or oligomeric amyloid ¦Â (oA¦Â) was measured by ELISA. The neuroprotective effects of MFG-E8 and MFG-E8£¿£¿£¿induced microglial phagocytosis of oA¦Â were assessed by immunocytochemistry. The effects of MFG-E8 on the production of the anti-oxidative enzyme hemeoxygenase-1 (HO-1) were determined by ELISA and immunocytochemisty.MFG-E8 was induced in microglia treated with conditioned medium from neurons that had been exposed to neurotoxicants, glutamate or oA¦Â. MFG-E8 significantly attenuated oA¦Â-induced neuronal cell death in a primary neuron£¿£¿£¿microglia coculture system. Microglial phagocytosis of oA¦Â was accelerated by MFG-E8 treatment due to increased CD47 expression in the absence of neurotoxic molecule production, such as tumor necrosis factor-¦Á, nitric oxide, and glutamate. MFG-E8£¿£¿£¿treated microglia induced nuclear factor E(2)£¿£¿£¿related factor 2 (Nrf2)£¿£¿£¿mediated HO-1 production, which also contributed to neuroprotection.These results suggest that microglia release MFG-E8 in response to signals from degenerated neurons and that MFG-E8 protects oA¦Â-induced neuronal cell death by promoting microglial phagocytic activity and activating the Nrf2-HO-1 pathway. Thus, MFG-E8 may have novel roles as a neuroprotectant in neurodegenerative conditions.
%K Microglia
%K Neuroprotection
%K MFG-E8
%K Nrf2
%U http://www.jneuroinflammation.com/content/9/1/148/abstract