NOS2 and Alzheimer disease: However, aberrantly activated microglia significantly increase neuroinflammation and neurotoxicity by secreting various pro-inflammatory cytokines and mediators including TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6), NO, reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), and COX-2 etc., which can lead to neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), cerebral ischemia, multiple sclerosis, and stroke [4–8].