LATE-ONSET PARKINSONISM AND PREMOTOR PATHOLOGY IN NF-KB/C-REL-DEFICIENT MICE (Abstract/Poster in convegno)

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Label
  • LATE-ONSET PARKINSONISM AND PREMOTOR PATHOLOGY IN NF-KB/C-REL-DEFICIENT MICE (Abstract/Poster in convegno) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • M. Pizzi(1), C. Baiguera(2), A. Pinna(3), A. Bellucci(4), M.A. De Luca(4), L. Frau(5), M. Morelli(4), R. Ingrassia(1), M. Benarese(2), A. Porrini(2), A. Lanzillotta(2), M. Pellitteri(6), G. Bertini(6), P.F. Fabene(6), M.G. Spillantini(7), H.C. Liou(8), P.F. Spano(1) (2014)
    LATE-ONSET PARKINSONISM AND PREMOTOR PATHOLOGY IN NF-KB/C-REL-DEFICIENT MICE
    in 9th FENS Forum of Neuroscience, Milano, 5-9 Luglio
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • M. Pizzi(1), C. Baiguera(2), A. Pinna(3), A. Bellucci(4), M.A. De Luca(4), L. Frau(5), M. Morelli(4), R. Ingrassia(1), M. Benarese(2), A. Porrini(2), A. Lanzillotta(2), M. Pellitteri(6), G. Bertini(6), P.F. Fabene(6), M.G. Spillantini(7), H.C. Liou(8), P.F. Spano(1) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://fens2014.meetingxpert.net/FENS_427/poster_103574/program.aspx (literal)
Note
  • Abstract (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • (1)Molecular and Translational Medicine, University of Brescia, Brescia, Italy ; (2)Molecular and Translational Medicine, University o Brescia, Brescia, Italy ; (3)CNR, University of Cagliari, Department of Biomedical Science, Italy ; (4)Department of Biomedical Science, University of Cagliari, Cagliari, Italy ; (5)Department of Biomedical Science, University of Cagliari, Brescia, Italy ; (6)Department of Neurological Neuropsychological Morphological and Motor Sciences, University of Verona, Verona, Italy ; (7)Department of Clinical Neurosciences Brain Repair Centre, University of Cambridge, Cambridge, Italy ; (8)Department of Immunology Weill Medical College, Cornell University, New York, Italy (literal)
Titolo
  • LATE-ONSET PARKINSONISM AND PREMOTOR PATHOLOGY IN NF-KB/C-REL-DEFICIENT MICE (literal)
Abstract
  • Nigrostriatal dopamine (DA) neuron degeneration, synaptic dysfunctions and neuroinflammation are among the key pathological features of Parkinson?s disease (PD). NF-kB factors are considered cardinal players in the progression of the neurodegenerative process, with dual effect on inflammation and apoptosis. While NF-kB/RelA factor is responsible for the commencement of apoptotic gene expression, NF-kB/c-Rel factor promotes transcription of anti-apototic genes, MnSOD, Bcl-xL and UCP4. Aim: To investigate possible age-associated neurodegeneration in c-rel-/- mice. Methods: WT and c-rel-/- mice were analyzed at 2, 12 and 18 months of age for their motor behavior, brain neurochemistry and pathology Results: At 18 months, c-rel-/- mice develop DA neuronal loss in substantia nigra pars compacta (SNc) with accumulation of aggregated alpha-synuclein and iron, microglia activation and a motor dysfunction. Motor deficits, occurring as hypo-motility and gait disorders, were responsive to L-DOPA administration. More recently we have found that a pathology characterized by alpha-synuclein accumulation in the dorsal nucleus of vagus and locus coeruleus, as well as striatal loss of dopamine transporter, is already present at a premotor age (12 months), making these mice a suitable model to investigate therapeutic approaches for early intervention in PD. Furthermore, blood mononuclear cells (PBMC) of selected PD patients display significantly reduced c-Rel activity. Conclusions: c-Rel factor is a regulator of SNc resilience to aging. Mice deficient for c-Rel represent an innovative animal model to study either premotor pathology and pathological progression of PD. It discloses a possible new diagnostic and therapeutic target deserving further investigation in PD patients. (literal)
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