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Cell Cycle. 2014;13(8):1335-44. doi: 10.4161/cc.28295. Epub 2014 Mar 4.

Involvement of peroxisome proliferator-activated receptor β/δ (PPAR β/δ) in BDNF signaling during aging and in Alzheimer disease: possible role of 4-hydroxynonenal (4-HNE).

Author information

  • 1Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
  • 2Department of Science-LIME; Roma Tre University; Rome, Italy.
  • 3Department of Biology; University of Rome "Tor Vergata"; Rome, Italy.
  • 4Department of Medical and Surgical Sciences and Neurosciences; University of Siena; Siena, Italy; Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology; Temple University; Philadelphia, PA USA.
  • 5Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy; Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology; Temple University; Philadelphia, PA USA.

Abstract

Aging and many neurological disorders, such as AD, are linked to oxidative stress, which is considered the common effector of the cascade of degenerative events. In this phenomenon, reactive oxygen species play a fundamental role in the oxidative decomposition of polyunsaturated fatty acids, resulting in the formation of a complex mixture of aldehydic end products, such as malondialdehyde, 4-hydroxynonenal, and other alkenals. Interestingly, 4-HNE has been indicated as an intracellular agonist of peroxisome proliferator-activated receptor β/δ. In this study, we examined, at early and advanced AD stages (3, 9, and 18 months), the pattern of 4-HNE and its catabolic enzyme glutathione S-transferase P1 in relation to the expression of PPARβ/δ, BDNF signaling, as mRNA and protein, as well as on their pathological forms (i.e., precursors or truncated forms). The data obtained indicate a novel detrimental age-dependent role of PPAR β/δ in AD by increasing pro-BDNF and decreasing BDNF/TrkB survival pathways, thus pointing toward the possibility that a specific PPARβ/δ antagonist may be used to counteract the disease progression.

KEYWORDS:

BDNF; JNK; TrkB; aging; neurodegenerative disease; oxidative stress; p75; transcription factors

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