More recently, a growing body of studies has provided evidence that derangement of insulin signaling underlying type-2 diabetes significantly increase the risk of cognitive impairment and Alzheimers disease (AD) progression (12). On this ground, the direct administration of STZ in the brain (i.e., by intracerebroventricular (ICV) infusion) has been used to develop an animal model of brain insulin resistance to mimic in rodents the pathophysiology of sporadic AD, which represents the most common form of AD in humans. STZ infusion in the brain induced accumulation of Amyloid beta (Aβ) protein (13), oxidative stress and cognitive impairment (14). Notably, there is now evidence that STZ infusion within the brain produced up-regulation of amyloid precursor protein (APP), tau hyperphosphorylation and neuroinflammation (15). This study (15), also shows that treatment with the cleavage-specific anti-tau 12A12 monoclonal antibody (mAb) can relieve APP upregulation, neuroinflammation and reduce cerebral oxidative stress, mitochondrial impairment, synaptic and histological alterations, as well as induce a nearly complete recovery of cognitive impairment in the STZ-induced SAD mouse model. Streptozotocin is now long off patent and many generic formulations are available. Biosynthesis
Recent advancements in understanding the biosynthesis of this natural product have been made by Balskus et al. In short, the authors found the gene cluster responsible for production of Streptozotocin in Streptomyces achromogenes and identified novel function of a non-heme iron enzyme, SznF, which forms the N-N bond in the N-nitrosourea pharmacophore by oxidative rearrangement. See also
Alloxan

References
12. Velayudhan, L. et al. Risk of developing dementia in people with diabetes and mild cognitive impairment. Br.
J. Psychiatry 2010, 196, 36–40. 13. Knezovic, A.; Osmanovic-Barilar, J.; Curlin, M.; Hof, P.R. ; Šimić, G.; Riederer, P.; Salkovic-Petrisic, M. et al. Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimers disease. J. Neural Transm. 2015, 122, 577–592. 14. Sharma, M. et al. Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci. 2001, 68, 1021–1029. 15. Latina, V. et al., Tau Cleavage Contributes to Cognitive Dysfunction in Streptozotocin-Induced Sporadic Alzheimers Disease (sAD) Mouse Model. Int. J. Mol. Sci. 2021, 22, 12158. https://doi.org/10.3390/ijms222212158. External links
U.S. Patent 3,027,300
FDA drug details