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INIZIO_TESTO_DA_INDICIZZARE

Fund for investing in fundamental research

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Research Units
  • Universita' degli Studi di CATANIA
    Dip. SCIENZE CHIMICHE , CATANIA (CT)
  • CENTRO INTERUNIVERSITARIO DI RICERCA SUI PEPTIDI BIOATTIVI (CIRPEB)
    CIRPEB , NAPOLI (NA)
  • Universita' degli Studi di BOLOGNA
    Dip. FISIOLOGIA UMANA E GENERALE , BOLOGNA (BO)
  • Universita' degli Studi G.D'Annunzio di CHIETI
    Dip. SCIENZE BIOMEDICHE , GENOVA (GE)
  • Universita' degli Studi di ROMA "Tor Vergata"
    Dip. BIOLOGIA , ROMA (RM)
  • Universita' degli Studi INSUBRIA Varese-Como
    Dip. BIOLOGIA STRUTTURALE E FUNZIONALE , VARESE (VA)
  • I.R.C.C.S. I.N.M. NEUROMED
    Neurobiologia e Neurofarmacologia , ISERNIA (IS)
  • Universit¿ degli Studi di GENOVA
    ONCOLOGIA, BIOLOGIA E GENETICA , GENOVA (GE)
  • Universita' degli Studi G.D'Annunzio di CHIETI
    Dip. SCIENZE BIOMEDICHE , CHIETI (CH)
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Bibliografia
Abraham E.H. et al. Blood Cells Mol. Dis. 27: 165-180, 2001
Acquati F. et al. FEBS Lett 468: 59-64, 2000
Ashner M. et al. Neurotoxicology 19: 7-17, 1998
Beckman J.S. et al. Am J. Physiol. 271: C1424-C1437, 1996
Berkenbosch F. et al. J. Neurosci. Res. 25: 431-440, 1990
Bernardi P. et al. Trends Biochem. Sci., 26 (2), 112-7, 2001
Billeter M. et al. Proc. Natl. Acad. Sci. USA, 94: 7281-7285, 1997
Blasko I. et al. Neurobiol. Dis. 7: 682-689, 2000
Bredt D.S. Free Rad. Res. 31: 577-596, 1999
Brown D.R. et al. Nature, 390: 684-687, 1997
Brown D.R., Besinger A. Biochem. J. 334: 423-429, 1998
Bruno V. et al. J. Neurosci., 18: 9594-9600, 1998
Caciagli F. et al. Pharmacol. Res.20: 935-947, 1988
Carrì M.T. et al. FEBS letters 414, 365-368, 1997
Caspi S. et al. J. Biol. Chem., 273: 3484-3489, 1998
Caughey B., G.J. Raymond, J. Virol., 67: 643-650, 1993
Caughey W.S. et al. Proc. Natl. Acad. Sci. USA, 95: 12117-12122, 1998
Cedazo-Minguez A. et al., Neuroscience 105: 651-661, 2001
Ciccarelli R. et al. Glia 25: 93-98, 1999a
Ciccarelli R. et al. Glia 27: 275-281, 1999b
Ciccarelli R. et al. Glia 29: 202-211, 2000
Cohen F. et al. Science 264: 530-531, 1994
Crompton M. et al. Biochem J. 341: 233-49, 1999
de Ceballos ML. et al. Clin. Chem. Lab. Med. 39: 317-318, 2001
Decleves X. et al. J. Neurosci. Res. 60: 594-601, 2000
De Pinto V.et al. Biochim. Biophys. Acta 894: 109-119, 1987
Di Iorio P. et al. Drug Dev. Res. 52: 303-315, 2001
Diringer H, Ehlers B, J. Gen. Virol., 72: 457-460, 1991
Donne D.G. et al. Proc. Natl. Acad: Sci. USA, 94: 13452-13457, 1997
Drouet B. et al. Cell.Mol.Life. Sci 57: 705-715
Ehlers B. Diringer H., J. Gen. Virol., 65: 1325-1330, 1984
Eisen A. Muscle & Nerve 18: 741-752, 1995
Estevez A.G. et al. Science 286: 2498-2500, 1999
Farquhar C.F, Dickinson A.G. J. Gen. Virol., 67: 463-473, 1986
Farzan M. et al. Proc.Natl.Acad.Sci.USA 97: 9712-9717, 2000
Ferrante R.J. et al. J.Neurochem. 69: 2064-2074, 1997
Ferri, A. et al. J.Neurochem. 75: 606-613, 2000
Florio T. et al. Biochem Biophys Res Commun 228: 397-405, 1996
Forloni G.et al. Nature 362: 543-546, 1993
Fukumoto H. et al. Neuroreport 10: 2965-2969, 1999
Gabbianelli R. et al. J.Neurochem. 73, 1175-1180, 1999
Garcia J.H. et al. Am J. Pathol. 142: 623-635, 1993
Harkany T. et al. Eur. J. Neurosci. 12: 2735-2745, 2000
Haydon P.G. Nature Rev. 2: 185-193, 2001
Hollo Z. et al. FEBS Lett. 383: 99-104, 1996
Hutton L.A. and Perez-Polo J.R. J. Neurosci. Res. 41: 185-196, 1995
Iarlori C. et al. J. Neuroimmunol. 107:100, 2000
James T.L. et al. Proc. Natl. Acad. Sci. USA, 94: 10086-10091, 1997
Janus J. et al. BBA 1502: 63-75, 2000
Kimberlin R.H, Walker C.A, Arch. Virol., 78: 9-18, 1983, Antimicrob. Agents
Knouff C. et al. J. Clin. Invest. 103. 1579-86, 1999
Korth C. et al. Proc. Natl. Acad. Sci. USA, 98: 9836-9841, 2001
Krieger C. et al. TIPS 17: 114-119, 1996
Kuroda Y. et al. J. Am. Chem. Soc., 122: 12596-12597, 2000
Lam FC. et al. J. Neurochem. 76: 1121-1128, 2001
Leroy E. et al. Nature 395: 451-452, 1998
Li Y. et al. Mol. Brain Res. 28:164-168, 1995
Lin C.-L.G. et al. Neuron 20: 589-602, 1998
Lin J.L. et al. Nature Neurosci. 1:494-500, 1998
Lipton P. Physiol. Rev. 79: 1431-1568, 1999
Liu R. et al. Ann.Neurol. 44: 763-770, 1998
Liu H. et al. Biochemistry, 38: 5362-5377, 1999
Lopez Garcia F. et al. Proc. Natl. Acad. Sci. USA, 97: 8334-8339, 2000
Chemother, 30: 409-413, 1986
MacFarlane S.N, Sontheimer H., Glia 30: 39-48, 2000
Mayeux R. et al. Ann. Neurol. 34: 752-754, 1993
McCord J.M. Sem. Hematol. 35: 5-12, 1998
McKeon R.J. et al. Exp. Neurol. 148: 558-567, 1997
Mennicken F. et al. Trends Pharmacol. Sci. 20: 73, 1999
Merlini G. et al. Proc. Natl. Acad. Sci. USA, 92: 2959-2963, 1995
Miroy G.J. et al. Proc. Natl. Acad. Sci. USA, 93: 15051-15056, 1996
Neary J.T. et al. TINS 19: 13-18, 1996
Okuizumi K. et al. Nat. Genet. 7: 10-11, 1994
Orrell R.W. Neuromuscular Disord, 10: 63-68, 2000
Oropeza RL. et al. Brain Res. 410: 45-51, 1987
Pan K. et al. Proc Natl Acad Sci U S A. 90:10962-10966, 1993
Peretz D. et al. Nature, 412: 739-74, 2001
Perrier V. et al. Proc. Natl. Acad. Sci. USA, 97: 6073-6078, 2000
Petito C.K. et al. J. Neuropathol. Exp. Neurol. 57: 231-238, 1998
Pocchiari M. et al. J. Gen Virol., 68: 219-223, 1987
Price D. et al. Ann.Rev.Genet 32: 461-493, 1998
Priola S.A. et al. Science 287: 1503-1506, 2000
Prusiner S. et al. Science 216:136-144, 1982
Prusiner S., Procl. Natl. acad. Sci. USA, 95:13363-13383, 1998
Rabizadeh S. et al. Proc. Natl. Acad. Sci USA. 92: 3024-3028, 1994
Rehncrona S. et al. J. Neurochem. 38: 84-93, 1982
Requena J.R. et al. Proc. Natl. Acad. Sci. USA, 98: 7170-7175, 2001
Ridet J.L., Malhotra S.K., Privat A and Gage F.H. TINS 20: 570-577, 1997
Riek R. et al. Nature, 382: 180-182, 1996
Riek R. et al. FEBS Lett., 413: 282-288, 1997
Riek R. et al. Proc. Natl. Acad. Sci. USA, 95: 11667-11672, 1998
Rohlff C. and Glazer RI. Int. J. Oncol. 12: 383-386, 1998
Rudge J.S. et al. Eur. J. Neurosci. 6: 693-705, 1994
Russo C. et al. Nature (London) 405: 531-532, 2000
Russo C. et al. .Neurobiol. Disease, 8, (1) part b, 173-180, 2001
Saido T.C. et al. Neuron 14, 457-466, 1995
Scemes E. et al. J. Neurosci. 15: 1435-1445, 2000
Seabrook G et al. Neuropharmacol 38: 1-17, 1999
Selkoe D.et al. Trends Cell Biol 8: 447-453, 1998
Selkoe D.J. et al. Physiol. Rev. 81: 741-766, 2001
Sharp F.R. et al. J. Cereb. Blood Flow Metab.20: 1011-1032, 2000
Shimizu S. et al. Nature. 399: 483-7, 1999
Shimura H. et al. Nat. Genet. 25: 302-305, 2000
Simpson J.E.et al. J. Neuroimmunol. 84: 238, 1998
Sinha S et al. Nature 402: 537-540, 1999
Sisodia S. et al. J.Clin.Invest 104: 1169-1170
Soto C. J. Mol. Med. 77: 412-418, 1999 and references therein.
Soto C. et al. Lancet, 355: 192-197, 2000
Sun et al. J. Neurosci. 18: 3261-72, 1998
Supattapone S. et al. Proc. Natl. Acad. Sci. USA, 96: 14529-14534, 1999
Tagliavini F. et al. Procl. Natl. Acad. Sci. USA. 90, 9678-9682, 1993
Tagliavini F. et al. Cell 79: 695-703, 1994
Tagliavini F. et al. Science, 276: 1119-1122, 1997
Tagliavini F. et al. J. Mol. Biol., 300: 1309-1322, 2000
Tanzi R.J.et al. Clin.Invest 104: 1175-1179,1999
Thellung S. et al. Neurobiol Disease 7: 299-309, 2000
Trotti D. et al. Nature Neurosci. 2: 427-433,1999
van Leuven F.et al. Prog. Neurol 61: 305-312, 2000
Vassar R. et al. Science 286: 735-741, 1999
Werner E.D. et al. Proc. Natl Acad. Sci. USA 93: 13797-13801, 1996
Wiedau-Pazos M. et al. Science 271: 515-518, 1996
Wisniewski T. et al. Lancet 345: 956-958, 1995
Von Eckardstein A. et al. FASEB J. 15: 1555-1561, 2001
Yan R. et al. Nature 402: 533-537, 1999
Yokoyama M., Black I.B. and Dreyfus C.F. Exp. Neurol. 124:377-380, 1993
Yu A.C. et al. Glia 35: 121-130, 2001
Yu S.P. et al. Curr. Opin. Cell Biol. 13: 405-411, 2001
Zahn R. et al. Proc. Natl. Acad. Sci., 97: 145-150, 2000
Zambrano N. et al. J. Biol. Chem. 272: 6399-6405, 1997
Zambrano N. et al. J Biol Chem. 276: 19787-19792, 2001
Keywords
antioxidant drugs; antifibrillogenic drugs; secretase inhibitors; chemokines; conformational diseases; glia

Development of innovative molecules for the treatment of neurodegenerative and neuroinflammatory disease

Università degli Studi di Catania
Abstract
This project is aimed to develop four promising therapeutic strategies based on the use of novel synthetic compounds for the treatment of neurodegenerative and neuroinflammatory diseases. Advanced experimental models (cell cultures and transgenic animals) will be used to test activity and efficacy and a better definition of the molecular targets will derive from the analysis of the pathogenetic mechanism responsible for neuronal degeneration in the same experimental models.
1) Development of molecules with an antioxidant activity able to exert a therapeutic action in neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer's disease. Based on the potential metal chelating, antioxidant and anti-fibrillogenic combined activities, novel mono- and bi functionalized b-cyclodextrins with carnosine will be synthesized and characterized. This strategy will be extended to the low molecular weight sugar, threalose, found to have antiaggregatory properties on proteins, stabilizing their folded conformations in cells subjected to oxidative stress. New compounds will be synthesized functionalizing this sugar with carnosine or carcinine. In addition, bioconjugated containing non-steroidal anti-inflamatory drugs will also be syntesized.
2) Design of new molecules for in vitro studies and in vivo studies based on the structural characterization of the prion, beta-amyloid and amylin peptides (and of their complexes), of miniprion recombinant product, and>>>

Principal Investigator
DANIELE FILIPPO CONDORELLI, Universita' degli Studi di CATANIA
Research Goal
This project is based on the following strategies for the development of potential drugs for the treatment of neurodegenerative and neuroinflammatory diseases;
Aim 1 - Synthesis and structural characterization of fibrillogenic peptides and their interactions with metallic ions, design and synthesis of new molecules able to antagonize the effects of misfolded protein or to decrease the fibrillogenesis process.
Aim 2 - Development of molecules with an antioxidant activity able to exert a therapeutic action in neurodegenerative diseases, such as ALS and Alzheimer's disease. A number of papers and patents describe b-AH as a potential drug able to protect against oxidative stress and related diseases, including ocular disorders. Exogenous carnosine does not accumulate in tissues and it is destroyed by carnosinase, a very specific dipeptidase present in the plasma, in the brain as well as in the liver and the kidneys. The functionalisation of carnosine with cyclodextrin (CDs) may make it possible to stabilize the carnosine while maintaining its biological and pharmaceutical properties. Furthermore, we have recently shown that b-cyclodextrin is an efficient scavenger of OH radicals. Thus we plan to synthesize mono- and bi funcionalized b-cyclodextrins with carnosine. Due to the recent report on the b-CD antiaggregatory ability on Ab peptides, this class of bioconjugates could show metal chelating, antioxidant and anti-aggregatory combined activities. This strategy>>>

Timescale
36 months