RICERCA ITALIANA     

Programmi di ricerca simili:

• 1 - Identificazione e caratterizzazione di mutazioni di geni coinvolti nell'ipertermia maligna e nel central core disease.
• 2 - Meccanismi di controllo dell’eritropoiesi e policitemie congenite e familiari: ruolo delle vie di risposta alla pressione di ossigeno
• 3 - Fisiopatologia delle lipoproteine plasmatiche ad alta densità (HDL): un approccio integrato
• 4 - Paraparesi spastiche ereditarie: studio genetico, funzionale, clinico
• 5 - Un approccio integrato allo studio della eziopatogenesi delle mitocondriopatie
• 6 - Variabilità e funzione delle mutazioni mitocondriali in condizioni fisiologiche e patologiche
• 7 - Genetica, biologia e clinica dei paragangliomi: le mutazioni della succinodeidrogenasi mitocondriale come modello di studio della trasmissione, crescita, variabilità e trattamento dei tumori di derivazione dalla cresta neurale
• 8 - Identificazione, analisi molecolare ed attività funzionale di recettori di membrana e fattori citoplasmatici coinvolti nella crescita e differenziamento di cellule di leucemia linfatica cronica B: impatto sulla prognosi clinica.
• 9 - Implicazioni diagnostico-terapeutiche delle nuove conoscenze cliniche e molecolari del carcinoma midollare della tiroide.
• 10 - IL SISTEMA MELANOCORTINICO NELL'OBESITA' E NEI DISTURBI DEL COMPORTAMENTO ALIMENTARE: MODELLI ANIMALI, SCREENING MOLECOLARE, CARATTERIZZAZIONE CLINICA E FUNZIONALE.

Classificazione scientifico-disciplinare

• Area scientifico disciplinare: Scienze mediche
  • GENETICA MEDICA
  • PATOLOGIA GENERALE
  • MEDICINA INTERNA

Classificazione brevettuale

• CHEMISTRY; METALLURGY
  • BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

Classificazione geografica

• Regione: Lombardia

Bibliografia

1) Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (ATP-III): final report. Circulation 106: 3143-421, 2002

2)Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke.systemic review and meta-analysis. BMJ 326: 1423-7, 2003

3)Rao DC, Laskarzewski PM, Morrison Ja et al. The Cincinnati Lipid Research Clinic family study. Cultural and biological determinants of lipids and lipoprotein concentrations Am J Hum Genet 34: 888-903, 1982

4)Heller DA, de Faire U, Pedersen NL et al. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med 328: 1150-56, 1993

5) Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia. New insights in pathogenesis and treatment. J Clin Invest 111: 179-1803, 2003

6)Dedussis GV, Schmidt H, Genschel J. LDL-receptor mutations in Europe. Hum Mutat 24: 443-59, 2004

7)Bertolini S, Cantafora A, Averna M, Cortese C, Motti C et al. Clinical Expression of familial hypercholesterolemia in clusters of mutations of the LDL receptor gene that cause a receptor-defective or receptor-negative phenotype. Arterioscler Thromb Vasc Biol 20: E41-52, 2000

8)Abifadel M, Varret M, Rabes JP, Allard D. et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet 34 : 154-6, 2003.

9)Seidah NG, Benjannet S, Wickman L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proc. Natl Acad. Sci. 100: 928-33, 2003

10) Naureckiene S, Ma L, Sreekumar K, et al. Functional characterization of Narc1, a novel proteinase related to proteinase K. Arch Biochem Biophys. 420:55-67, 2003.

11)Leren TP. Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia. Clin Genet 65:419-22, 2004

12)Timms KM, Wagner S, Samuels ME, Forbey K. et al. A mutation in PCSK9 causing autosoma-dominant hypercholesterolemia in a Utah pedigree. Hum Genet 114: 349-53, 2004

13) Naoumova RP, Tosi I, Patel D, Neuwirth C, Horwell SD, et al. Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow up and treatment response. Arterioscler Thromb Vasc Biol 25: 2654-60, 2005

14) Allard D, Amsellem S, Abifadel et al. Novel mutations in the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Hum Mutat 26: 497, 2005 (mutation in brief ,e1-e9)
15) Pisciotta L, Oliva CP, Cefalù AB, Noto D. Bellocchio A., Fresa R, et al. Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia. Atherosclerosis (in press) (Epub Sept21)

16)Maxwell KN, Breslow JL. Adenoviral-mediated expression of Pcsk9 in mice results in a low density lipoprotein receptor knockout phenotype. Proc Natl Acad Sci 101: 7100-5, 2004

17)Park SW, Moon YA, Horton JD. Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver. J Biol Chem 279: 50630-8, 2004

18)Bejannet S, Rhainds D, Essalmani R, et al. NARC-1/PCSK9 and its natural mutants : zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol. J Biol Chem 279: 48865-75, 2004

19)Schonfeld G, Lin X, Yue P. Familial hypobetalipoproteinemia: genetic and metabolism. Cell Mol Life Sci 62: 1372-78, 2005

20)Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat Genet 37: 161-5, 2005

21) Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, et al. Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9. Proc Natl Acad Sci 102: 5374-9, 2005

22) Kotowski IK, Pertsemlidis A, Luke A, Cooper RS, Vega GL, et al. A spectrum of PCSK9 alleles contributes to plasma levels of low density lipoprotein cholesterol. Am J Hum Genet 78: 410-22, 2006

23) Berge KE, Ose L, Leren TP. Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy. Arterioscler Throm Vasc Biol (in press) (Epub Jan 19, 2006)

24) Horton JD, Shah NA, Warrington JA, Anderson NN, Park SW, Brown MS, Golstein JL.
Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identified direct SREBP target genes. Proc Natl Acad. Sci 100: 12027-12032, 2003

25) Maxwell KN, Soccio RE, Duncan EM, Sehayek E, Breslow JL. Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol fed-mice. J Lipid Res 44: 2109-2119, 2003.

26) Maxwell KN, Breslow IL Proprotein convertase subtilisin kexin 9: the third locus implicated in autosomal dominant hypercholesterolemia. Curr Opin Lididol 16: 167-72, 2005


27)Lalanne F. Lambert G. Amar MJ, Chetiveaux M, Zairt Y, et al. Wild type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells. J Lipid Res 46: 1312-9, 2005

28)Maxwell KN, Fisher EA, Breslow JL. Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci 102: 2069-74, 2005

29) Sun XM, Eden ER, Tosi I, Neuwirth CK, Wile D. Naoumova RP, Soutar AK. Evidence for effect of mutant PCSK9 on apolipoprotein B secretion as the cause of unusually severe dominant hypercholesterolemia. Hum Mol Genet 14: 1161-9, 2005

30)Ouguerram K, Chetiveaux M, Zair Y, Costet P, Abifadel M, Varret M, et al. Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9. Arterioscler Tromb Vasc Biol 24: 1448-53, 2004

31)Dubuc G, Chamberland A, Wassef H, Davignon J, Seidah NG, Bernier L, Prat A. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 24: 1454-9, 2004

32) Basak A. Inhibitors of proprotein convertases. J Mol Med 83: 844-55, 2005

33) Lambert G, Krempf M, Costet P. PCSK9: a promising therapeutic target for dyslipidemias?
Trends in Endocrinology and Metabolism (in press).

34)Cohen JC, Boerwinkle E, Mosley TH, Hobbs HH. Sequence variants in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354: 1264-72, 2006

Parole Chiave

IPERCOLESTEROLEMIA, IPOCOLESTEROLEMIA, GENE PCSK9, ESPRESSIONE ALLELI MUTANTI, MUTAZIONI LOF E GOF, ESPRESSIONE GENICA, STATINE, ATEROSCLEROSI