ABSTRACT Several studies have reported a relation between increased pro-inflammatory mediators such as TNF-α and apoptosis in neurodegenerative diseases such as Alzheimer’s disease (AD). It is known that lipopoly-saccharide (LPS) treatment induces neuroinflammation and memory deterioration, and it has been reported that LPS induces apoptosis mostly through the production of TNF-α. Pentoxifylline (PTX), is a vascular protective agent and a potent TNF-alpha inhibitor. However, the molecular neuroprotective mechanisms of PTX against LPS-induced neurotoxicity have not been well studied. In this study, we investigated the direct protective effect of PTX against LPS-induced toxicity in Rat pheochromocytoma (PC12) cell line. The results showed that a pretreatment with PTX prior exposure to LPS signifycantly decreased LPS-induced cell death. Mechanisms study showed that PTX has the potential to inhibit pro-inflammatory and pro-apoptotic pathways via the suppression of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. This is the first study to report the anti-inflammatory and anti-apoptotic effects of PTX via inhibition of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. Altogether, these observations indicate that PTX is capable of promoting neuroprotective effects, meanwhile also present some insights into the potential signaling pathways that are involved. Thus, these findings support the potential for PTX to be investigated as a potential agent for the treatment of neurodegenerative diseases such as AD.
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