Alzheimer's disease (AD) is the result of a combination of genetic and environmental risk factors and the molecular mechanisms underlying cognitive decline are yet to be fully elucidated. The so-called "amyloid cascade hypothesis" has long been the prevailing paradigm for causation of disease, and today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and lipid and glucose dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the CNS and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes, PPARα is known to be either downregulated or activated under pathological conditions, including AD. Several lines of in vitro and in vivo evidence emphasize possible treatment of amyloid pathology based on PPARα natural or synthetic ligands. This review provides an update on this topic, focussing on the effects of selective agonists in modulating neuronal/glial processes, involved in AD onset and progression. Anti-amyloidogenic properties of fibrates in humans and in mouse models of pathological ageing, as well as protective action of this class of FDA-approved xenobiotics against Aβ-induced neuronal damage suggest their therapeutic use in delaying AD progression. At the same time, endogenous PPARα ligands, such as N-acyl ethanolamines, may even prevent memory decline and secretion of pro-inflammatory molecules, as demonstrated in different pathological models. Overall, targeting PPARα to elicit antioxidant response, blunt neuroinflammation, and promote survival vs. neurodegeneration mechanisms, appears a promising and timely approach to AD treatment.
D. Orio, B., Fracassi, A., Cerù, M.P., & Moreno, S. (2018). Targeting PPARalpha In Alzheimer`s Disease. CURRENT ALZHEIMER RESEARCH, 15(4), 345-354 [10.2174/1567205014666170505094549].
|Titolo:||Targeting PPARalpha In Alzheimer`s Disease|
MORENO, Sandra (Corresponding)
|Data di pubblicazione:||2018|
|Citazione:||D. Orio, B., Fracassi, A., Cerù, M.P., & Moreno, S. (2018). Targeting PPARalpha In Alzheimer`s Disease. CURRENT ALZHEIMER RESEARCH, 15(4), 345-354 [10.2174/1567205014666170505094549].|
|Appare nelle tipologie:||1.1 Articolo in rivista|