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 language | English (US) |
|---|---|
| Pages (from-to) | 1-10 |
| Number of pages | 10 |
| Journal | Current Alzheimer Research |
| Volume | 15 |
| Issue number | 4 |
| DOIs | |
| State | Published - Jan 1 2018 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Targeting PPARalpha in Alzheimer's disease
AU - D'Orio, Barbara
AU - Fracassi, Anna
AU - Cerù, Maria Paola
AU - Moreno, Sandra
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Energy metabolism
KW - Fibrates
KW - Neuroinflammation
KW - Oxidative stress
KW - PEA
KW - Peroxisome proliferator activated receptors
KW - β-amyloid
UR - http://www.scopus.com/inward/record.url?scp=85048995581&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048995581&partnerID=8YFLogxK
U2 - 10.2174/1567205014666170505094549
DO - 10.2174/1567205014666170505094549
M3 - Article
VL - 15
SP - 1
EP - 10
JO - Current Alzheimer Research
JF - Current Alzheimer Research
SN - 1567-2050
IS - 4
ER -