Inflammatory processes have been shown to be involved in development and progression of neurodegenerative diseases. Mammalian target of rapamycin (mTOR) involves in various cellular processes including autophagy, apoptosis and energy metabolism. Recently, studies have been shown an association between mTOR pathway and inflammation, supporting the role of the pathway in the pathogenesis of inflammatory disorders including neurodegenerative diseases. There are several studies have been shown that rapamycin, an antagonist of mTOR pathway, or PF-4708671, a mTOR substrate inhibitor, exhibits high neuroprotective effects through reducing inflammation. For example, rapamycin attenuates proinflammatory responses by increasing anti-inflammatory activity of regulatory T cells to restrain post-stroke neuro-inflammation. Moreover, pharmacological inhibition of mTOR decreases neuronal inflammation in cerebral palsy mice model subjected to hypoxia-ischemia and lipopolysaccharide-induced inflammation. Similarly, Liu et al indicated that inhibition of mTOR inhibits amyloid-β or LPS-induced neuro-inflammation in mice models. Consistent with the anti-inflammatory effects of mTOR inhibitors, Ding et al, reported that melatonin negatively regulates the release of proinflammatory cytokines by inhibition of the mTOR in traumatic brain injury in animal models. Taken together, these results clearly suggest that mTOR inhibitors can be considered as a promising therapeutic target to suppress neuronal inflammation in neurodegenerative diseases. Understanding of the exact molecular mechanism of mTOR signaling could be helpful to design a novel mTOR inhibitor to regulate the inflammatory responses in neurodegenerative diseases.

The human amniotic membrane known as the innermost single epithelial-covered layer provides many applications such as applicable anti-inflammatory and anti-cancer effects. These immunomodulatory effects belongs to the epithelial cells, a type of epiblast-derived fetal stem cells which currently used for regenerative medicine and transplantation. These cells are collected by author-prepared facilities and expanded in 75 cm2 cell culture flask (Biofil) in the DMEM, 12% FBS and penicillin-streptomycin antibiotic incubated in 80% humidity, 5% CO2 for 72 hours. These cell released the special macromolecules modulate the inflammatory pathways so the 2×105 cells were expanded in the 25 cm2 flask and incubated in the standard incubation condition. After 72 hours, the media changed and after 5 days, the cellular supernatant were collected as the conditioned media. The U937 cell line were treated with 50% condition media and standard medium (RPMI 1640, 5% GlutaMax and 10% FBS) for one week. The level of mRNA expression of IL1α and β and IL 8 were evaluated in the U937 cells after 1 week treatment with conditioned media. The obtained results illustrated the significant reduction in the IL1α and β and IL 8 cellular expression in the treated cells (p<0.001). The conditioned medium obtained from expanded human amniotic membrane epithelial cells has the anti-inflammatory effects based on obtained results on U937 cell line. This properties may provide the promising way in regenerative medicine.