title: Axonal PPARγ promotes neuronal regeneration after injury.
abstract: PPARγ is a ligand-activated nuclear receptor best known for its involvement in adipogenesis and glucose homeostasis. PPARγ activity has also been associated with neuroprotection in different neurological disorders, but the mechanisms involved in PPARγ effects in the nervous system are still unknown. Here we describe a new functional role for PPARγ in neuronal responses to injury. We found both PPAR transcripts and protein within sensory axons and observed an increase in PPARγ protein levels after sciatic nerve crush. This was correlated with increased retrograde transport of PPARγ after injury, increased association of PPARγ with the molecular motor dynein, and increased nuclear accumulation of PPARγ in cell bodies of sensory neurons. Furthermore, PPARγ antagonists attenuated the response of sensory neurons to sciatic nerve injury, and inhibited axonal growth of both sensory and cortical neurons in culture. Thus, axonal PPARγ is involved in neuronal injury responses required for axonal regeneration. Since PPARγ is a major molecular target of the thiazolidinedione (TZD) class of drugs used in the treatment of type II diabetes, several pharmaceutical agents with acceptable safety profiles in humans are available. Our findings provide motivation and rationale for the evaluation of such agents for efficacy in central and peripheral nerve injuries.
authors.affiliation: Department of Physiology, Millenium Nucleus in Regenerative Biology (MINREB) and CARE Center, Pontificia Universidad Católica De Chile, Santiago, Chile.|Department of Cellular and Molecular Biology, CARE Center, Pontificia Universidad Católica De Chile, Santiago, Chile.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lezana
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Shachar Y
authors.initials: SY
authors.lastname: Dagan
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Ari
authors.initials: A
authors.lastname: Robinson
authors.affiliation: Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 52900, Israel.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Goldstein
authors.affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, 76100, Israel.
authors.forename: Mike
authors.initials: M
authors.lastname: Fainzilber
authors.affiliation: Department of Physiology, Millenium Nucleus in Regenerative Biology (MINREB) and CARE Center, Pontificia Universidad Católica De Chile, Santiago, Chile.
authors.forename: Francisca C
authors.initials: FC
authors.lastname: Bronfman
authors.affiliation: Department of Cellular and Molecular Biology, CARE Center, Pontificia Universidad Católica De Chile, Santiago, Chile.
authors.forename: Miguel
authors.initials: M
authors.lastname: Bronfman
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D019771:Axotomy; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000473:pathology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D047495:PPAR gamma; C051774:neurofilament protein H
keywords: PPARγ; axon; dynein; regeneration; retrograde transport