000061281 001__ 61281
000061281 005__ 20190709135451.0
000061281 0247_ $$2doi$$a10.1073/pnas.1610586114
000061281 0248_ $$2sideral$$a98209
000061281 037__ $$aART-2017-98209
000061281 041__ $$aeng
000061281 100__ $$aPerni, M.
000061281 245__ $$aA natural product inhibits the initiation of a-synuclein aggregation & suppresses its toxicity
000061281 260__ $$c2017
000061281 5060_ $$aAccess copy available to the general public$$fUnrestricted
000061281 5203_ $$aThe self-Assembly of a-synuclein is closely associated with Parkinson''s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects a-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces a-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of a-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing a-synuclein, observing a dramatic reduction of a-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson''s disease and related conditions.
000061281 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/RYC-2012-12068
000061281 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000061281 590__ $$a9.504$$b2017
000061281 591__ $$aMULTIDISCIPLINARY SCIENCES$$b5 / 64 = 0.078$$c2017$$dQ1$$eT1
000061281 592__ $$a6.092$$b2017
000061281 593__ $$aMultidisciplinary$$c2017$$dQ1
000061281 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000061281 700__ $$aGalvagnion, C.
000061281 700__ $$aMaltsev, A.
000061281 700__ $$aMeisl, G.
000061281 700__ $$aMüller, M.B.D.
000061281 700__ $$aChalla, P.K.
000061281 700__ $$aKirkegaard, J.B.
000061281 700__ $$aFlagmeier, P.
000061281 700__ $$aCohen, S.I.A.
000061281 700__ $$aCascella, R.
000061281 700__ $$aChen, S.W.
000061281 700__ $$aLimboker, R.
000061281 700__ $$aSormanni, P.
000061281 700__ $$aHeller, G.T.
000061281 700__ $$aAprile, F.A.
000061281 700__ $$0(orcid)0000-0002-9138-6687$$aCremades, N.$$uUniversidad de Zaragoza
000061281 700__ $$aCecchi, C.
000061281 700__ $$aChiti, F.
000061281 700__ $$aNollen, E.A.A.
000061281 700__ $$aKnowles, T.P.J.
000061281 700__ $$aVendruscolo, M.
000061281 700__ $$aBax, A.
000061281 700__ $$aZasloff, M.
000061281 700__ $$aDobson, C.M.
000061281 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000061281 773__ $$g114, 6 (2017), E1009-E1017$$pProc. Natl. Acad. Sci.$$tProceedings of the National Academy of Sciences$$x0027-8424
000061281 8564_ $$s3085978$$uhttps://zaguan.unizar.es/record/61281/files/texto_completo.pdf$$yVersión publicada
000061281 8564_ $$s40560$$uhttps://zaguan.unizar.es/record/61281/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000061281 909CO $$ooai:zaguan.unizar.es:61281$$particulos$$pdriver
000061281 951__ $$a2019-07-09-11:40:44
000061281 980__ $$aARTICLE