title: 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).
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.
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Benedetti
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: D'Angelo
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Cristiano
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Di Giacomo
authors.affiliation: Department of Science-LIME; Roma Tre University; Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
authors.affiliation: Department of Science-LIME; Roma Tre University; Rome, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moreno
authors.affiliation: Department of Biology; University of Rome "Tor Vergata"; Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fidoamore
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antonosante
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Falcone
authors.affiliation: Department of Life, Health, and Environmental Sciences; University of L'Aquila; Coppito L'Aquila, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ippoliti
authors.affiliation: Department 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.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department 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.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cimini
mesh_terms: D000375:Aging / Q000378:metabolism*; D000447:Aldehydes / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D048068:PPAR-beta / Q000819:agonists / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D020813:Receptor, trkB
chemical_list: D000447:Aldehydes; D019208:Brain-Derived Neurotrophic Factor; D051549:Glutathione S-Transferase pi; D008562:Membrane Glycoproteins; D047494:PPAR delta; D048068:PPAR-beta; D011505:Protein-Tyrosine Kinases; C064371:Ntrk2 protein, mouse; D020813:Receptor, trkB; C027576:4-hydroxy-2-nonenal
keywords: BDNF; JNK; TrkB; aging; neurodegenerative disease; oxidative stress; p75; transcription factors