damage associated with shi and tbi. stroke according to the national stroke association, stroke is the third-leading cause of death and the leading cause of adult disability. it is thought that glutamate levels cause underlying ischemic damage during a stroke, and, thus, naag inhibition might be able to diminish this damage. schizophrenia schizophrenia is a mental disorder that affects 1% of people throughout the world. it can be modeled by pcp in laboratory animals, and it has been shown that mglur agonists have reduced the effects of the drug. naag is such an mglur agonist. thus, inhibition of the enzyme that reduces naag concentration, naag peptidase, could provide a practical treatment for reduction of schizophrenic symptoms. diabetic neuropathy diabetes can lead to damaged nerves, causing loss of sensation, pain, or, if autonomic nerves are associated, damage to the circulatory, reproductive, or digestive systems, among others. over 60% of diabetic patients are said to have some form of neuropathy, however, the severity ranges dramatically. neuropathy not only directly causes harm and damage but also can indirectly lead to such problems as diabetic ulcerations, which in turn can lead to amputations. in fact, over half of all lower limb amputations in the united states are of patients with diabetes. through the use of the naag peptidase inhibitor 2-pmpa, naag cleavage was inhibited and, with it, programmed drg neuronal cell death in the presence of high glucose levels. the researchers have proposed that the cause of this is naag's agonistic activity at mglur3. in addition, naag also “prevented glucose-induced inhibition of neurite growth” (berent- spillson, et al. 2004). overall, this makes gcpiii inhibition a clear model target for combating diabetic neuropathy. drug addiction schizophrenia, as previously described, is normally modeled in the laboratory through a pcp animal model. as gcpiii inhibition was shown to possibly limit schizophrenic behavior in this model, this suggests that gcpiii inhibition, thus, reduces the effect of pcp. in addition, the reward action of many drugs (cocaine, pcp, alcohol, nicotine, etc.) have been shown with increasing evidence to be related to glutamate levels, on which naag and gcpiii can have some regulatory effect. in summary, the findings of multiple drug studies to conclude that: naag/np system might be involved in neuronal mechanisms regulating cue-induced cocaine craving, the development of cocaine seizure kindling, and management of opioid addiction and alcohol consumptive behaviour. therefore, np inhibitors could provide a novel therapy for such conditions. other diseases and disorders naag inhibition has also been studied as a treatment against prostate cancer, als, and other neurodegenerative diseases such as parkinson's disease and huntington's disease.