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)

Elisabetta Benedetti, Barbara D'Angelo, Loredana Cristiano, Erica Di Giacomo, Francesca Fanelli, Sandra Moreno, Francesco Cecconi, Alessia Fidoamore, Andrea Antonosante, Roberta Falcone, Rodolfo Ippoliti, Antonio Giordano, Annamaria Cimini

Research output: Contribution to journalArticlepeer-review

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 PPAR β/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.

Original languageEnglish
Pages (from-to)1335-1344
Number of pages10
JournalCell Cycle
Volume13
Issue number8
DOIs
Publication statusPublished - Apr 15 2014

Keywords

  • Aging
  • BDNF
  • JNK
  • Neurodegenerative disease
  • Oxidative stress
  • p75
  • Transcription factors
  • TrkB

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Fingerprint

Dive into the research topics of '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)'. Together they form a unique fingerprint.

Cite this