Nutrition-Based Modulation of Poly-ADP-Ribosylation and its Possible Role In Alzheimer's Disease

Alzheimer's Disease (AD) is the most common neurodegenerative disease and the main reason of dementia in the elderly. On the pathological point of view, it is characterized by extracellular aggregates of amyloid peptides and intracellular deposits of tau protein. These deposits affect neuron viability and functions by inducing (among other pathological pathways) oxidative stress and triggering mitochondrial dysfunction. It is now evident that free radicalinduced oxidative damage is strongly involved in the pathogenesis of AD. Oxidative damage occurs early in disease pathogenesis and can exacerbate its progression. Post-mortem brain of individuals affected by AD, evidenced an extensive state of oxidative stress compared to healthy controls; markers of increased oxidation include, among others, DNA damage. DNA damage can induce the activity of the enzyme poly (ADP-ribose) polymerase 1 (PARP-1) that catalyze the reaction of poly (ADP-ribosylation). This post-translational modification modulates the functions of proteins involved in many physiological processes such as gene expression, maintenance of genomic stability and cell death. Therefore, inhibiting PARP-1 activity can represent a possible new strategy to reduce the impact of the oxidative stress in AD as well as in other neurodegenerative diseases. Here we discuss the role of nutrients in modulating PARP-1 activity and its perspective potential application.