Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer's disease and other tauopathies(72 visite) Florenzano F, Veronica C, Ciasca G, Ciotti MT, Pittaluga A, Olivero G, Feligioni M, Iannuzzi F, Latina V, Sciacca MFM, Sinopoli A, Milardi D, Pappalardo G, De Spirito M, Papi M, Atlante A, Bobba A, Borreca A, Calissano P, Amadoro G
Impact factor: 5.168, Impact factor a 5 anni: 5.312
Url: Non disponibile.
Parole chiave: Alzheimer, S Disease, Extracellular Tau, Immunotherapy, Neurodegeneration, Synapse(s), Tau Cleavage,
Affiliazioni:
*** IBB - CNR *** European Brain Research Institute, Rome, Italy., Institute of Translational Pharmacology, CNR, Rome, Italy., Institute of Physics, Catholic University of the Sacred Heart, Rome, Italy., Institute of Cellular Biology and Neuroscience, CNR, IRCSS Santa Lucia Foundation, Rome, Italy., Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, Viale Cembrano, Italy., Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy., Institute of Biostructures and Bioimaging, CNR, Catania, Italy., Institute of Biomembranes and Bioenergetics, CNR, Bari, Italy.,
Riferimenti:
Non disponibile.
The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH2-derived fragments of protein on synaptic dysfunction underlying neurodegenerative tauopathies, including Alzheimer's disease (AD). Here we show that sub-toxic doses of extracellular-applied human NH2tau 26-44 (aka NH2htau) -which is the minimal active moiety of neurotoxic 20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma- acutely provokes presynaptic deficit in K+-evoked glutamate release on hippocampal synaptosomes along with alteration in local Ca2+ dynamics. Neuritic dystrophy, microtubules breakdown, deregulation in presynaptic proteins and loss of mitochondria located at nerve endings are detected in hippocampal cultures only after prolonged exposure to NH2htau. The specificity of these biological effects is supported by the lack of any significant change, either on neuronal activity or on cellular integrity, shown by administration of its reverse sequence counterpart which behaves as an inactive control, likely due to a poor conformational flexibility which makes it unable to dynamically perturb biomembrane-like environments. Our results demonstrate that one of the AD-relevant, soluble and secreted N-terminally truncated tau forms can early contribute to pathology outside of neurons causing alterations in synaptic activity at presynaptic level, independently of overt neurodegeneration.
Antonini A, Vitale C, Barone P, Cilia R, Righini A, Bonuccelli U, Abbruzzese G, Ramat S, Petrone A, Quatrale R, Marconi R, Ceravolo R, Stefani A, Lopiano L, Zappia M, Capus L, Morgante L, Tamma F, Tinazzi M, Colosimo C, Guerra UP, Valzania F, Fagioli G, Distefano A, Bagnato A, Feggi L, Anna S, Maria Teresa Rosaria De Cr, Nobili F, Mazzuca N, Baldari S, Eleopra R, Bestetti A, Benti R, Varrone A, Volterrani D, Massa R, Stocchi F, Schillaci O, Dore F, Zibetti M, Castellano G, Battista SG, Giorgetti G * The relationship between cerebral vascular disease and parkinsonism: The VADO study(158 visite) Parkinsonism Relat Disord (ISSN: 1353-8020, 1873-5126, 1873-5126electronic), 2012; 18(6): 775-780. Impact Factor:3.274 DettagliEsporta in BibTeXEsporta in EndNote
Bruni AC, Bernardi L, Colao R, Rubino E, Smirne N, Frangipane F, Terni B, Curcio SA, Mirabelli M, Clodomiro A, Di Lorenzo R, Maletta R, Anfossi M, Gallo M, Geracitano S, Tomaino C, Muraca MG, Leotta A, Lio SG, Pinessi L, Rainero I, Sorbi S, Nee L, Milan G, Pappata S, Postiglione A, Abbamondi N, Forloni G, St George Hyslop P, Rogaeva E, Bugiani O, Giaccone G, Foncin JF, Spillantini MG, Puccio G * Worldwide distribution of PSEN1 Met146Leu mutation: A large variability for a founder mutation(112 visite) Neurology (ISSN: 0028-3878, 1526-632x, 1526-632xelectronic), 2010 Mar 9; 74(10): 798-806. Impact Factor:8.017 DettagliEsporta in BibTeXEsporta in EndNote
187 Records (161 escludendo Abstract e Conferenze). Impact factor totale: 725.125 (637.09 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 760.605 (655.076 escludendo Abstract e Conferenze).
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