Title : Neuroprotective Mechanisms of Nicotinamide Adenine Dinucleotide and Related Precursors in Alzheimer’s Disease
In the current aging society, the number of patients suffering from Alzheimer’s disease (AD) is rapidly increasing, and without therapeutic breakthroughs is estimated to reach 80 million by 2040. As an irreversible chronic neurodegenerative disease, AD is characterized by progressive cognitive deficits, memory loss, and personality changes taking place with advancing age. Synaptic dysfunction, and especially the degeneration of cholinergic neurons, also leads to cognitive impairment and deficits in memory and learning and in emotional resilience. Oxidative stress, apoptosis, inflammation, autophagy, and mitochondrial dysfunction have also been widely shown to be involved in the progress of the disease. Thus, it seems that novel multi-targeted treatments are needed to prevent or slow disease progressive. Nicotinamide adenine dinucleotide (NAD+) is a crucial cofactor involved in a wide spectrum of biological functions including oxidative phosphorylation, mitochondrial function and bioenergetics, cell proliferation, and calcium homeostasis. Also, NAD+ is essential for appropriate function and survival in the central nervous system. Sudies showed that NAD+ precursors appeared to be an effective anti-AD strategy for preventing neuropathological and behavioral symptoms induced by AD in preclinical trials. Such favorable effects are possibly modulated by reducing central Aβ and tau levels and improving brain bioenergetics, inflammation, and oxidative stress regulation.