Louwerse et al. (1995) reported a double-blind trial of NAC in 111 patients with ALS. Patients with limb onset but not bulbar onset of ALS had a 50% decrease in the 1 year mortality rate after beginning NAC treatment (Cray et al. 1980; May and Gray 1985; Louwerse et al. 1995). Parkinson’s disease Multiple neuronal systems are involved in sporadic PD. Alpha-synuclein-immunopositive Lewy neurites and Lewy bodies are the cardinal histopathology in PD. Lesions initially occur in the dorsal motor nucleus of the glossopharyngeal and vagal nerves and anterior olfactory nucleus. Anteromedial temporal mesocortex is involved too. Neural degeneration in substantia nigra, which is Inhibitors,research,lifescience,medical a common finding
in sporadic PD, could be a coincidental finding rather than a casual finding (Braak et al. 2003). Increased lipid peroxidation and dramatically Inhibitors,research,lifescience,medical decreased GSH levels have been reported in PD (Arakawa and Ito 2007). Some published reports have mentioned that GSH levels were
reduced by 40% in substantia nigra compared to controls (Sian et al. 1994). Decreased GSH levels may be due to mitochondrial dysfunction and oxidative stress. Oxidative stress will increase the accumulation of toxic forms of alpha-synuclein (SNCA). Simon and his team hypothesized that supplementation with NAC could protect against SNCA toxicity. They found that in transgenic mice, Inhibitors,research,lifescience,medical NAC increases the SN levels of GSH within 5–7 weeks of treatment; however, this increase was not sustained at 1 year. Despite this transient Inhibitors,research,lifescience,medical effect, they found that the loss of dopaminergic terminals at 1 year associated with SNCA overexpression was significantly
attenuated by NAC supplementation (Clark et al. 2010). Dopaminergic neuronal death in PD is BIIB057 in vitro accompanied by oxidative stress and preceded by GSH depletion. Earlier studies confirmed that mice have age-dependent loss of dopaminergic neurons in pars compacta of Inhibitors,research,lifescience,medical the substantia nigra (Jiang et al. 2005). This neuronal loss is accompanied by increased nitrotyrosine formation, nitrosylated many a-synuclein, and microglial activation. These changes are considerably reduced in mice that received NAC. Martinez et al. hypothesized that treatment with a sulfur-containing antioxidant such as NAC may provide a new neuroprotective therapeutic strategy for PD (Schapira et al. 1990; Martínez et al. 1999). Generation of hydrogen peroxide by monoamino oxidase (MAO) and ROS production by catecholamines in the substantia nigra are other precipitating factors in PD (Martínez et al. 1999). Moreover, the substantia nigra in PD patients is rich in iron and in neuromelanin, two other sources that may mediate the formation of ROS. Clinical trials using antioxidants such as vitamin E (The Parkinson Study Group 1993; Pappert et al. 1996) and vitamin C for the treatment of PD have been reported (Reilly et al. 1983).
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