Alzheimer's Disease, a Lipid Story: Involvement of Peroxisome Proliferator-Activated Receptor alpha

Saez-Orellana, Francisco; Octave, Jean-Noel; Pierrot, Nathalie


Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Mutations in genes encoding proteins involved in amyloid-beta peptide (A beta) production are responsible for inherited AD cases. The amyloid cascade hypothesis was proposed to explain the pathogeny. Despite the fact that A beta is considered as the main culprit of the pathology, most clinical trials focusing on A beta failed and suggested that earlier interventions are needed to influence the course of AD. Therefore, identifying risk factors that predispose to AD is crucial. Among them, the epsilon 4 allele of the apolipoprotein E gene that encodes the major brain lipid carrier and metabolic disorders such as obesity and type 2 diabetes were identified as AD risk factors, suggesting that abnormal lipid metabolism could influence the progression of the disease. Among lipids, fatty acids (FAs) play a fundamental role in proper brain function, including memory. Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a master metabolic regulator that regulates the catabolism of FA. Several studies report an essential role of PPAR alpha in neuronal function governing synaptic plasticity and cognition. In this review, we explore the implication of lipid metabolism in AD, with a special focus on PPAR alpha and its potential role in AD therapy.

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Título según WOS: ID WOS:000539340200149 Not found in local WOS DB
Título de la Revista: CELLS
Volumen: 9
Número: 5
Editorial: MDPI
Fecha de publicación: 2020


Notas: ISI