Agonist Gnrh

Studies of cell culture models could provide mechanistic insights into the protective effects of NAC in the animal models.Thus, NAC administration to primary cortical neuron cultures decreased activity of typical signal transduction pathways that mediate cell death, including the MLKJNK pathway. Buildup of betaamyloid molecules leads to plaque formation in AD, and the betaamyloid is generated by secretasecatalyzed cleavage of amyloid precursor protein. Accordingly, limiting APP protein formation would be expected to decrease plaque formation.NAC administration was found to inhibit APP transcription to almost undetectable levels in SHSYY cells; unfortunately, changes in the protein expression were not measured. The promising results of NAC in cell culture and mouse models of AD have led to human studies.Administration of mgkgday of NAC daily for the duration of the study resulted in Glipizide favorable changes in some but not all cognitive measurements in human volunteers. Although these studies represent a small subset of patients, they warrant consideration of a broader study to verify the effectiveness of NAC in AD.The underlying mechanism through which the expressed mutant huntingtin protein causes neuronal degeneration is still unclear, but oxidative damage has been implicated by post mortem studies reporting an Sertraline hydrochloride increase in oxidized cellular components. HD patients have decreased GSH content in plasma samples compared to age matched controls. Ideally, cell culture lines could be generated from neurons taken from HD and nonHD individuals.Animal models of HD have given a small glimpse into what may occur in HD patients.Oddly, the HD mouse model R showed a significant increase in GSH content in the mitochondria isolated from the cortex and striatum. The authors hypothesize that the increased GSH could be a compensatory mechanism for increased ROS production, although the authors did not specifically measure ROS or other products of oxidative stress.Rats treated with nitropropionic acid showed a decrease in total GSH and a decrease in GST function in the striatum, hippocampus, and cortex. Specific levels of GSH in the mitochondria of the brain sections were not measured; hence it is unknown if these rats had changes in mitochondrial GSH consistent with what was previously reported. However in vitro use of huntingtin knockin striatal cell lines indicates that the depletion of GSH can be blocked by the administration of cystamine prior to NP.This stabilization of GSH content resulted in less cell death.Importantly, BSO treatment in conjunction with cystamine resulted in no increase in cell survival strongly suggesting that normal GSH levels are the mediating survival factor. However, the mechanism by which maintenance or supplementation of GSH could protect against HD remain to be elucidated.While human subjects are not conducive to studying disease mechanisms, HD mouse lines are available that have not been exploited thoroughly in this regard.Different SOD mutations have been shown to result in distinct pathology.All three distinct mutations result in neurodegeneration; however, it is intriguing that none of the mutations results in loss of enzyme function.Nevertheless, there are some differences among the mice bearing different SOD mutations.Clearly, different mutations in SOD result in distinct pathogenesis.This is an important topic of discussion, and a more in depth review focusing on the biology of ALS including differences in SOD models is available.

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