Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer’s agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults. Pathogenic factors, such as oxidative stress, an increase in acetylcholinesterase activity, mitochondrial dysfunction, genotoxicity, and neuroinflammation are present in this syndrome, which leads to neurodegeneration. Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic, epigenetic, and environmental factors. There are two main types of Alzheimer’s disease, known as familial Alzheimer’s disease (onset < 65 years) and late-onset or sporadic Alzheimer’s disease (onset ≥ 65 years). Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) genes in an autosomal-dominantly fashion with closely 100% penetrance. In contrast, a different picture seems to emerge for sporadic Alzheimer’s disease, which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology. Importantly, the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation. However, the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans. In recent years, there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease. Through epigenetic mechanisms, such as DNA methylation, non-coding RNAs, histone modification, and chromatin conformation regulation, natural compounds appear to exert neuroprotective effects. While we do not purport to cover every in this work, we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.