J. Broers, F. Ramaekers, and G. Bonne, Nuclear Lamins: Laminopathies and Their Role in Premature Ageing, Physiological Reviews, vol.86, issue.3, pp.967-1008, 2006.
DOI : 10.1152/physrev.00047.2005

URL : http://physrev.physiology.org/content/physrev/86/3/967.full.pdf

W. Schmidt, A. Tam, and K. Fujimura-kamada, Endoplasmic reticulum membrane localization of Rce1p and Ste24p, yeast proteases involved in carboxyl-terminal CAAX protein processing and amino-terminal a-factor cleavage, Proceedings of the National Academy of Sciences, vol.13, issue.22, pp.11175-80, 1998.
DOI : 10.1016/0092-8674(93)90639-8

E. Choy, V. Chiu, and J. Silletti, Endomembrane Trafficking of Ras, Cell, vol.98, issue.1, pp.69-80, 1999.
DOI : 10.1016/S0092-8674(00)80607-8

I. Firmbach-kraft and R. Stick, Analysis of nuclear lamin isoprenylation in Xenopus oocytes: isoprenylation of lamin B3 precedes its uptake into the nucleus, The Journal of Cell Biology, vol.129, issue.1, pp.17-24, 1995.
DOI : 10.1083/jcb.129.1.17

G. Bonne, D. Barletta, M. Varnous, and S. , Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy, Nature Genetics, vol.21, issue.3, pp.285-293, 1999.
DOI : 10.1038/6799

S. Zinn-justin, Maladies g??n??tiques et lamines de type A : apport de la biologie structurale, m??decine/sciences, vol.18, issue.11, pp.1054-1059, 2002.
DOI : 10.1051/medsci/200218111054

URL : http://www.medecinesciences.org/articles/medsci/pdf/2002/09/medsci20021811p1054.pdf

J. Lammerding, P. Schulze, and T. Takahashi, Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction, Journal of Clinical Investigation, vol.113, issue.3, pp.349-51, 2004.
DOI : 10.1172/JCI200419670

URL : http://www.jci.org/articles/view/19670/files/pdf

D. Lloyd, R. Trembath, and S. Shackleton, A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies, Human Molecular Genetics, vol.11, issue.7, pp.769-77, 2002.
DOI : 10.1093/hmg/11.7.769

C. Navarro, P. Cau, and N. Levy, Molecular bases of progeroid syndromes, Human Molecular Genetics, vol.15, issue.suppl_2, pp.151-61, 2006.
DOI : 10.1093/hmg/ddl214

E. Markiewicz, T. Dechat, and R. Foisner, Lamin A/C Binding Protein LAP2alpha Is Required for Nuclear Anchorage of Retinoblastoma Protein, Molecular Biology of the Cell, vol.13, issue.12, pp.4401-4414, 2002.
DOI : 10.1091/mbc.E02-07-0450

G. Novelli, A. Muchir, and F. Sangiuolo, Mandibuloacral Dysplasia Is Caused by a Mutation in LMNA-Encoding Lamin A/C, The American Journal of Human Genetics, vol.71, issue.2, pp.426-457, 2002.
DOI : 10.1086/341908

D. Sandre-giovannoli, A. Bernard, R. Cau, and P. , Lamin A Truncation in Hutchinson-Gilford Progeria, Science, vol.300, issue.5628, p.2055, 2003.
DOI : 10.1126/science.1084125

C. Navarro, J. Cadinanos, D. Sandre-giovannoli, and A. , Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and accumulation of Lamin A precursors, Human Molecular Genetics, vol.14, issue.11, pp.1503-1516, 2005.
DOI : 10.1093/hmg/ddi159

C. Navarro, D. Sandre-giovannoli, A. Bernard, and R. , Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy, Human Molecular Genetics, vol.13, issue.20, pp.2493-503, 2004.
DOI : 10.1093/hmg/ddh265

URL : https://hal.archives-ouvertes.fr/hal-01668977

A. Agarwal, J. Fryns, and R. Auchus, Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia, Human Molecular Genetics, vol.12, issue.16, pp.1995-2001, 2003.
DOI : 10.1093/hmg/ddg213

URL : https://academic.oup.com/hmg/article-pdf/12/16/1995/6947753/ddg213.pdf

R. Goldman, D. Shumaker, and M. Erdos, Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome, Proceedings of the National Academy of Sciences, vol.200, issue.3, pp.8963-8971, 2004.
DOI : 10.1016/0076-6879(91)00127-I

T. Sullivan, D. Escalante-alcalde, and H. Bhatt, Loss of a-Type Lamin Expression Compromises Nuclear Envelope Integrity Leading to Muscular Dystrophy, The Journal of Cell Biology, vol.225, issue.5, pp.913-933, 1999.
DOI : 10.1083/jcb.137.6.1199

M. Bergo, B. Gavino, and J. Ross, Zmpste24 deficiency in mice causes spontaneous bone fractures, muscle weakness, and a prelamin A processing defect, Proceedings of the National Academy of Sciences, vol.102, issue.4, pp.13049-54, 2002.
DOI : 10.1002/ajmg.1463

A. Pendas, Z. Zhou, and J. Cadinanos, Defective prelamin A processing and muscular and adipocyte alterations in Zmpste24 metalloproteinase???deficient mice, Nature Genetics, vol.311, pp.94-103, 2002.
DOI : 10.1038/ng871

B. Liu, J. Wang, and K. Chan, Genomic instability in laminopathy-based premature aging, Nature Medicine, vol.278, issue.7, pp.780-785, 2005.
DOI : 10.1074/jbc.C300060200

I. Varela, J. Cadinanos, and A. Pendas, Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation, Nature, vol.4, issue.7058, pp.564-572, 2005.
DOI : 10.1016/S0960-9822(00)00002-6

L. Fong, J. Ng, and J. Lammerding, Prelamin A and lamin A appear to be dispensable in the nuclear lamina, Journal of Clinical Investigation, vol.116, issue.3, pp.743-52, 2006.
DOI : 10.1172/JCI27125

L. Fong, J. Ng, and M. Meta, Heterozygosity for Lmna deficiency eliminates the progeria-like phenotypes in Zmpste24-deficient mice, Proceedings of the National Academy of Sciences, vol.101, issue.28, pp.18111-18117, 2004.
DOI : 10.1073/pnas.0401424101

P. Scaffidi and T. Misteli, Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome, Nature Medicine, vol.7, issue.43, pp.440-445, 2005.
DOI : 10.1038/nbt964

L. Fong, D. Frost, and M. Meta, A Protein Farnesyltransferase Inhibitor Ameliorates Disease in a Mouse Model of Progeria, Science, vol.311, issue.5767, pp.1621-1624, 2006.
DOI : 10.1126/science.1124875

J. Pan, M. She, and Z. Xu, Farnesyltransferase Inhibitors Induce DNA Damage via Reactive Oxygen Species in Human Cancer Cells, Cancer Research, vol.65, issue.9, pp.3671-81, 2005.
DOI : 10.1158/0008-5472.CAN-04-2744

URL : http://cancerres.aacrjournals.org/content/canres/65/9/3671.full.pdf

E. Van-beek, E. Pieterman, and L. Cohen, Farnesyl Pyrophosphate Synthase Is the Molecular Target of Nitrogen-Containing Bisphosphonates, Biochemical and Biophysical Research Communications, vol.264, issue.1, pp.108-119, 1999.
DOI : 10.1006/bbrc.1999.1499

C. Coffinier, S. Hudon, and E. Farber, HIV protease inhibitors block the zinc metalloproteinase ZMPSTE24 and lead to an accumulation of prelamin A in cells, Proceedings of the National Academy of Sciences, vol.22, issue.22, pp.13432-13439, 2007.
DOI : 10.1093/emboj/cdg571

M. Caron, M. Auclair, and B. Donadille, Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence, Cell Death and Differentiation, vol.20, issue.10, pp.1759-67, 2007.
DOI : 10.1006/excr.2000.4823

P. Scaffidi and T. Misteli, Lamin A-Dependent Nuclear Defects in Human Aging, Science, vol.312, issue.5776, pp.1059-63, 2006.
DOI : 10.1126/science.1127168

J. Mazières, A. Pradines, and G. Favre, Les inhibiteurs de farn??syl transf??rase : une cible peut en cacher une autre, m??decine/sciences, vol.19, issue.2, pp.211-217, 2003.
DOI : 10.1051/medsci/2003192211

D. Langui, F. Lachapelle, and C. Duyckaerts, Mod??les animaux des maladies neuro-d??g??n??ratives, m??decine/sciences, vol.23, issue.2, pp.180-186, 2007.
DOI : 10.1051/medsci/2007232180

URL : http://www.medecinesciences.org/articles/medsci/pdf/2007/02/medsci2007232p180.pdf

I. Varela, S. Pereira, and A. Ugalde, Combined treatment with statins and aminobisphosphonates extends longevity in a mouse model of human premature aging, Nature Medicine, vol.154, issue.7, pp.767-72, 2008.
DOI : 10.1172/JCI200422087

URL : https://hal.archives-ouvertes.fr/inserm-00376425

H. Gilgenkrantz, Une nouvelle piste thérapeutique dans le traitement des syndromes progéroïdes, Med Sci (Paris), vol.24, p.819, 2008.

À. Retourner-À and E. , -E-mail : edk@edk.fr ISBN : 978-2-8425-4120-0 188 pages L'impasse du savoir : Prix public 18 ? + 3 ? de port = 21 ? TTC 'instauration des essais cliniques a été une révolution médicale de la seconde moitié du XX e siècle, 2008.

. La-nécessité-d, un nouveau mode d'acquisition du savoir en médecine est la thèse ici développée par Philippe Abastado