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Several small molecule inhibitors that can specifically bind to the BB loop of the TIR domain of TLR/RAGE have already been developed that are currently in various stages of clinical trial (see Table 2) but none has been licensed for use of NGDs (Figure 4, the primary cause of the neuronal death is because of chronic inflammatory response initiated due to release of NF-B

MedChemComm 10(9):15311544 Bennicia G, Almahasheer H, Alghrably M et al (2024) Mitigating diabetes associated with reactive oxygen species (ROS) and protein aggregation through Pharmacological interventions

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Figure 4 Mitochondrial superoxide is an important intracellular source of reactive oxygen species and plays a critical role in promoting Fenton/Haber-Weiss reactions by releasing iron from intracellular ferritin complex, which in turn culminates in the generation of highly reactive hydroxyl radicals (6973)

Finally, NETosis requires both oxidative burst and PAD4 activation, events are dispensable for apoptosis