On the other hand, NAC may cross the BBB (Martínez et al. 1999; Farr et al. 2003), and NAC exerts a preventive effect in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD (Pan et al. 2009). One ongoing randomized clinical

trial to evaluate the role of NAC as a neuroprotective agent in PD is currently recruiting participants (NCT01470027, http://www.clinicaltrials.gov). Further controlled trials involving administration of NAC or GSH precursors or in combination with other Pomalidomide mouse antioxidants are needed (Martínez et al. 1999). Alzheimer’s disease AD is a multifactorial disease. There is both direct and indirect evidence of free-radical involvement in AD. Increased Inhibitors,research,lifescience,medical levels of lipid peroxides in the temporal and cerebral cortex, and decreases in GSH in cortical areas and the hippocampus have been reported

in AD (Adams et al. 1991; Jenner 1994; Lohr and Browning 1995). Most clinical trials of antioxidants for the treatment of AD have employed either tocopherol (a class of chemical compounds which many Inhibitors,research,lifescience,medical have vitamin E activity) or selegiline (also known as l-deprenyl, an irreversible and relatively selective MAO-B inhibitor). NAC has been tested in some murine models of AD, and these studies provided supportive evidence that administration of NAC blocks Inhibitors,research,lifescience,medical oxidative damage in AD (Tchantchou et al. 2005; Tucker et al. 2005). Adair et al. (2001) administered NAC in a blinded placebo-controlled trial in patients with AD. In patients Inhibitors,research,lifescience,medical with clinically diagnosed AD, treatment with NAC failed to alter the primary outcome measures. However, the results may still support future testing of NAC in AD. First, all subjects tolerated the drug well, experiencing Inhibitors,research,lifescience,medical only minor and transient adverse effects. Second, the group taking NAC showed positive effects on some secondary outcome measures. Further testing of NAC in patients with AD may determine whether it provides more benefit than vitamin E and other

antioxidants (Adair et al. 2001). Beneficial effect of NAC after focal cerebral ischemia Cerebral ischemia alters the mitochondria leading to increased ROS generation (Morris et al. 2011). Initiation of the ischemic cascade affects not only neuronal signaling but also several humoral mediators and diverse humoral pathways including opioids, NO, adenosine, bradykinin, GBA3 catecholamines, heat-shock proteins, heme oxygenase, tumor necrosis factor-alpha (TNF-α), angiotensin, and prostaglandins (Vasdekis et al. 2013). Neural damage following stroke is promoted by a massive release of excitatory neurotransmitters such as glutamate that acts on the N-methyl-d-aspartate (NMDA) receptor and other receptor subtypes (Cuzzocrea et al. 2000b). Animal studies have shown that glutamate receptor antagonists reduce neuronal damage following ischemic stroke and reduce neurotoxicity (Cuzzocrea et al. 2000b).