Background:
The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be
fully elucidated. The so-called “amyloid cascade hypothesis” has long been the prevailing paradigm for
causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative
stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors
(PPARs) are expressed in the central nervous system (CNS) and regulate many physiological
processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle.
Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α
and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising
therapeutic target in AD.
Conclusion:
This review provides an update on this topic, focussing on the effects of natural or synthetic
agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated
PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation.
Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates
glucose and lipid dysmetabolism, and stimulates autophagy.
Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
