Targeting PPARalpha in Alzheimer's disease

Barbara D'Orio, Anna Fracassi, Maria Paola Cerù, Sandra Moreno

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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. 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. Ligand-activated 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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalCurrent Alzheimer Research
Volume15
Issue number4
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

PPAR alpha
Peroxisome Proliferator-Activated Receptors
Alzheimer Disease
Autophagy
Oxidative Stress
Physiological Phenomena
Amyloid
Synaptic Transmission
Causality
Energy Metabolism
Oxidation-Reduction
Cell Cycle
Homeostasis
Central Nervous System
Antioxidants
Ligands
Lipids
Glucose
Therapeutics

Keywords

  • Alzheimer's disease
  • Energy metabolism
  • Fibrates
  • Neuroinflammation
  • Oxidative stress
  • PEA
  • Peroxisome proliferator activated receptors
  • β-amyloid

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Targeting PPARalpha in Alzheimer's disease. / D'Orio, Barbara; Fracassi, Anna; Cerù, Maria Paola; Moreno, Sandra.

In: Current Alzheimer Research, Vol. 15, No. 4, 01.01.2018, p. 1-10.

Research output: Contribution to journalArticle

D'Orio, Barbara ; Fracassi, Anna ; Cerù, Maria Paola ; Moreno, Sandra. / Targeting PPARalpha in Alzheimer's disease. In: Current Alzheimer Research. 2018 ; Vol. 15, No. 4. pp. 1-10.
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