Especially, a majority of anti-oxidant natural compounds and neuroprotectants, including polyphenolic phytochemical exogenously, evokes NRF2-mediated hormetic response, thereby, effectively reducing the occurrence and severity of various neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease as well as ischemic stroke [88]. This evidence concerns the gene NFE2L2 and early-onset autosomal dominant Alzheimer disease.