The molecular and cellular pathology of α1-antitrypsin deficiency

Trends in Molecular Medicine

Volumn 20, Issue 2, 2014, Pages 116-127

  Gooptu, Bibek ^a,b   Dickens, Jennifer A ^c   Lomas, David A ^b,d  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF LONDON   (United Kingdom)

^c UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

1 antitrypsin deficiency; Cirrhosis; Conformational disease; Emphysema; Misfolding; Protein evolution

Indexed keywords

ALPHA 1 ANTITRYPSIN; BRONCHODILATING AGENT; MONOCLONAL ANTIBODY; OXYGEN; STEROID;

ALPHA 1 ANTITRYPSIN DEFICIENCY; APOPTOSIS; CELL PATHOLOGY; COMPUTER ASSISTED TOMOGRAPHY; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; CYTOLOGY; DENSITOMETRY; EMPHYSEMA; GAIN OF FUNCTION MUTATION; GENOTYPE ENVIRONMENT INTERACTION; HETEROZYGOTE ADVANTAGE; HUMAN; INFLAMMATION; LIVER CELL; LIVER DISEASE; LOSS OF FUNCTION MUTATION; LUNG DISEASE; MOLECULAR PATHOLOGY; NONHUMAN; PATHOGENESIS; PLURIPOTENT STEM CELL; PNEUMONIA; POLYMERIZATION; PROTEIN FOLDING; PROTEIN FUNCTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SMOKING; SMOKING CESSATION; UNFOLDED PROTEIN RESPONSE; CLINICAL FEATURE; DISEASE ASSOCIATION; ENDOPLASMIC RETICULUM ASSOCIATED DEGRADATION; GENE MUTATION; GENETIC VARIABILITY; LUNG ALVEOLUS MACROPHAGE; MODIFIER GENE; PHENOTYPE; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN POLYMERIZATION; PROTEIN SYNTHESIS; QUALITY CONTROL;

CIRRHOSIS; CONFORMATIONAL DISEASE; EMPHYSEMA; MISFOLDING; PROTEIN EVOLUTION; Α(1)-ANTITRYPSIN DEFICIENCY;

ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; ANIMALS; ENDOPLASMIC RETICULUM; HUMANS; PROTEIN MULTIMERIZATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOLYSIS; UNFOLDED PROTEIN RESPONSE;

EID: 84893667261     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2013.10.007     Document Type: Review

References (126)

1. 1-antitrypsin deficiency. Scand. J. Clin. Lab. Invest. 1963, 15:132-140.
2. 1X-Glykoprotein als chymotrypsin-inhibitor des humanplasmas. Clin. Chim. Acta 1965, 12:116-118.
3. 1-antitrypsin deficiency. Acta Med. Scand. 1965, 432(Suppl.):1-85.
4. 1-antitrypsin deficiency. Acta Med. Scand. 1964, 175:197-205.
5. Eriksson S. Emphysema before and after 1963 - historic perspectives. Ann. N. Y. Acad. Sci. 1991, 624:1-6.
6. 1-antitrypsin in human sera. Clin. Chim. Acta 1967, 16:199-203.
7. Lace B., et al. Age of SERPINA1 gene PI Z mutation: Swedish and Latvian population analysis. Ann. Hum. Genet. 2008, 72:300-304.
8. 1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: a comprehensive review. Ther. Adv. Respir. Dis. 2012, 6:277-295.
9. 1-antitrysin deficiency in Japan. Am. Rev. Respir. Dis. 1995, 152:2119-2126.
10. malton) in COPD patients from Eastern Tunisia. Biochem. Genet. 2013, 51:677-685.
11. Sharp H.L., et al. Cirrhosis associated with α-1-antitrypsin deficiency: a previously unrecognised inherited disorder. J. Lab. Clin. Med. 1969, 73:934-939.
12. 1-antitrypsin deficiency detected by screening of 200,000 infants. N. Engl. J. Med. 1976, 294:1316-1321.
13. 1-antitrypsin deficiency. N. Engl. J. Med. 1986, 314:736-739.
14. Carrell R.W., Gooptu B. Conformational changes and disease - serpins, prions and Alzheimer's. Curr. Opin. Struct. Biol. 1998, 8:799-809.
15. Carrell R.W., Lomas D.A. Conformational diseases. Lancet 1997, 350:134-138.
16. Gooptu B., Lomas D.A. Polymers and inflammation: disease mechanisms of the serpinopathies. J. Exp. Med. 2008, 205:1529-1534.
17. 1-proteinase inhibitor by human lung-derived epithelial cells. J. Biol. Chem. 1997, 272:8250-8255.
18. 1-antitrypsin by alveolar epithelial cells. FEBS Lett. 1994, 346:171-174.
19. Geboes K., et al. Morphological identification of α-1-antitrypsin in the human small intestine. Histopathology 1982, 6:55-60.
20. 1-antitrypsin. Am. J. Respir. Crit. Care Med. 1996, 154:1829-1833.
21. Cohen A.B. Interrelationships between the human alveolar macrophage and α-1-antitrypsin. J. Clin. Invest. 1973, 52:2793-2799.
22. 1-proteinase inhibitor. Biochem. Biophys. Res. Commun. 1980, 95:864-871.
23. Huntington J.A., et al. Structure of a serpin-protease complex shows inhibition by deformation. Nature 2000, 407:923-926.
24. 1-antitrypsin deficiency: molecular and cellular insights. Eur. Respir. J. 2009, 34:475-488.
25. Panyutich A.V., et al. Human neutrophil defensin and serpins form complexes and inactivate each other. Am. J. Respir. Cell Mol. Biol. 1995, 12:351-357.
26. 1-antitrypsin in the prevention of pulmonary emphysema. Am. J. Respir. Crit. Care Med. 2006, 173:1222-1228.
27. 1-antitrypsin accumulation in the liver. Nature 1992, 357:605-607.
28. Hekman C.M., Loskutoff D.J. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J. Biol. Chem. 1985, 260:11581-11587.
29. 1-antitrypsin by a peptide sequentially similar to β-strand s4A. Eur. J. Biochem. 1990, 194:51-56.
30. 1-proteinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J. Mol. Biol. 1984, 177:531-556.
31. Skinner R., et al. Implications for function and therapy of a 2.9Å structure of binary-complexed antithrombin. J. Mol. Biol. 1998, 283:9-14.
32. Jin L., et al. The anticoagulant activation of antithrombin by heparin. Proc. Natl. Acad. Sci. U.S.A. 1997, 94:14683-14688.
33. Fitton H.L., et al. Mechanisms of antithrombin polymerisation and heparin activation probed by insertion of synthetic reactive loop peptides. Biol. Chem. 1997, 378:1059-1063.
34. 1-antitrypsin related cirrhosis. J. Biol. Chem. 2002, 277:6771-6774.
35. Stein P.E., Carrell R.W. What do dysfunctional serpins tell us about molecular mobility and disease?. Nat. Struct. Biol. 1995, 2:96-113.
36. 1-antitrypsin. J. Biol. Chem. 1999, 274:9548-9555.
37. 1-antichymotrypsin indicates two stage insertion of the reactive loop; implications for inhibitory function and conformational disease. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:67-72.
38. Kroeger H., et al. Endoplasmic reticulum-associated degradation (ERAD) and autophagy cooperate to degrade polymerogenic mutant serpins. J. Biol. Chem. 2009, 284:22793-22802.
39. 1-antitrypsin variant are degraded within the endoplasmic reticulum by a mechanism sensitive to inhibitors of protein synthesis. J. Biol. Chem. 1992, 267:1072-1080.
40. 1-antitrypsin Z are propagated in the absence of autophagic activity. J. Biol. Chem. 2006, 281:4467-4476.
41. 1-antitrypsin that is retained within the rough endoplasmic reticulum. J. Biol. Chem. 1988, 263:7330-7335.
42. 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele. Am. J. Hum. Genet. 1994, 55:1113-1121.
43. 1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFκB, and BAP31 but not the unfolded protein response. J. Biol. Chem. 2005, 280:39002-39015.
44. 1-antitrypsin deficiency. Hepatology 2013, 57:2049-2060.
45. 1-antitrypsin deficiency. J. Immunol. 2004, 172:5722-5726.
46. 1-antitrypsin within the hepatic endoplasmic reticulum does not elevate the steady-state level of grp78/BiP. J. Biol. Chem. 1990, 265:20463-20468.
47. Davies M.J., et al. Neuroserpin polymers activate NF-κB by a calcium signaling pathway that is independent of the unfolded protein response. J. Biol. Chem. 2009, 284:18202-18209.
48. 1-antitrypsin deficiency. Am. J. Physiol. Gastrointest. Liver Physiol. 2004, 286:G851-G862.
49. Lindblad D., et al. α-1-Antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology 2007, 46:1228-1235.
50. 1-antitrypsin Z in endoplasmic reticulum is associated with an autophagic response. Am. J. Physiol. Gastrointest. Liver Physiol. 2000, 279:G961-G974.
51. Rudnick D.A., Perlmutter D.H. α-1-Antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology 2005, 42:514-521.
52. 1 Antitrypsin deficiency due to Pi null: clinical presentation and evidence for molecular heterogeneity. J. Med. Genet. 1988, 25:83-87.
53. Fregonese L., et al. α-1 Antitrypsin null mutations and severity of emphysema. Respir. Med. 2008, 102:876-884.
54. 1-antitrypsin without inhibition of elastase. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:15007-15012.
55. 1-antitrypsin Hum. Mol. Genet. 2013, 10.1093/hmg/ddt487.
56. 1-antitrypsin related emphysema. Am. J. Respir. Cell Mol. Biol. 1998, 18:670-674.
57. 1-antitrypsin co-localise with neutrophils in emphysematous alveoli and are chemotactic in vivo. Am. J. Pathol. 2005, 166:377-386.
58. 1-Antitrypsin polymerizes in the lung and acts as a neutrophil chemoattractant. Chest 2004, 125:1952-1957.
59. 1-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema. Am. J. Respir. Cell Mol. Biol. 2002, 26:723-730.
60. 1-antitrypsin deficiency. Am. J. Respir. Crit. Care Med. 2006, 10:1072-1077.
61. 1-antitrypsin deficiency. Lancet 1985, 1:152-154.
62. 1-antitrypsin deficiency associated with emphysema. N. Engl. J. Med. 1987, 316:1055-1062.
63. Gøtzsche P.C., Johansen H.K. Intravenous α-1 antitrypsin augmentation therapy: systematic review. Dan. Med. Bull. 2010, 57:A4175.
64. 1-Antitrypsin deficiency. N. Engl. J. Med. 2009, 360:2749-2757.
65. Ratner M. Cochrane meta-analysis on α-1-antitrypsin prompts furor. Nat. Biotechnol. 2010, 28:885-886.
66. Dickens J.A., Lomas D.A. Why has it been so difficult to prove the efficacy of α-1-antitrypsin replacement therapy? Insights from the study of disease pathogenesis. Drug Des. Dev. Ther. 2011, 5:391-405.
67. 1-antitrypsin deficiency. Eur. Respir. J. 2009, 33:1345-1353.
68. 1 antitrypsin deficiency (A1ATD); a randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 2013, 187. Abstract A6069.
69. 1-antitrypsin deficiency revealed by the structure of a domain-swapped trimer. EMBO Rep. 2011, 12:1011-1017.
70. Yamasaki M., et al. Crystal structure of a stable dimer reveals the molecular basis of serpin polymerization. Nature 2008, 455:1255-1258.
71. Nyon M.P., et al. Structural dynamics associated with intermediate formation in an archetypal conformational disease. Structure 2012, 20:504-512.
72. Ekeowa U.I., et al. Defining the mechanism of polymerization in the serpinopathies. Proc. Natl. Acad. Sci. U.S.A. 2010, 107:17146-17151.
73. 1-antitrypsin deficiency. Hepatology 2010, 52:1078-1088.
74. Gooptu B., Lomas D.A. Conformational pathology of the serpins: themes, variations and therapeutic strategies. Annu. Rev. Biochem. 2009, 78:147-176.
75. Janciauskiene S., et al. Detection of circulating and endothelial cell polymers of Z and wild type α-1-antitrypsin by a monoclonal antibody. J. Biol. Chem. 2002, 277:26540-26546.
76. 1-antitrypsin. Hepatology 2004, 40:1203-1210.
77. 1-antitrypsin deficiency-related panniculitis. Demonstration of skin polymers and high dosing requirements of intravenous augmentation therapy. Dermatology 2009, 218:370-375.
78. 1 antitrypsin and its polymers. Ann. Rheum. Dis. 2011, 70:1851-1856.
79. DeMeo D.L., et al. Circulating polymers of α-1 antitrypsin in PiZZ subjects. Am. J. Respir. Crit. Care Med. 2012, 185:A4361.
80. 1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema. Orphanet J. Rare Dis. 2011, 6:14.
81. Lockett A.D., et al. Effect of cigarette smoke exposure and structural modifications on the α-1 antitrypsin interaction with caspases. Mol. Med. 2012, 18:445-454.
82. 1-antitrypsin. Nature 1982, 298:329-334.
83. 1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema. Am. J. Physiol. Lung Cell. Mol. Physiol. 2009, 297:L388-L400.
84. 1-antitrypsin by cigarette smoke induces polymerization: a novel mechanism of early-onset emphysema. Am. J. Respir. Cell Mol. Biol. 2011, 45:261-269.
85. Mueller C., Flotte T.R. Gene-based therapy for α-1 antitrypsin deficiency. COPD 2013, 10:44-49.
86. Rashid S.T., et al. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J. Clin. Invest. 2010, 120:3127-3136.
87. Yusa K., et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 2011, 478:391-394.
88. McNab G.L., et al. Modification of gene expression and increase in α1-antitrypsin (α1-AT) secretion after homologous recombination in α1-AT-deficient monocytes. Hum. Gene Ther. 2007, 18:1171-1177.
89. Cruz P.E., et al. In vivo post-transcriptional gene silencing of α-1 antitrypsin by adeno-associated virus vectors expressing siRNA. Lab. Invest. 2007, 87:893-902.
90. Chang Y-P., et al. Targeting serpins in high-throughput and structure-based drug design. Methods Enzymol. 2011, 501:139-175.
91. Chang Y.P., et al. Small-molecule peptides inhibit Z α1-antitrypsin polymerization. J. Cell. Mol. Med. 2009, 13:2304-2316.
92. 1-antitrypsin. Am. J. Respir. Cell Mol. Biol. 2006, 35:540-548.
93. 1-antitrypsin: implications for disease and drug design. J. Mol. Biol. 2009, 387:857-868.
94. 1-antitrypsin to prevent conformational disease. J. Biol. Chem. 2003, 278:33060-33066.
95. 1-antitrypsin characterized at high resolution. Acta Crystallogr. Sect. F: Struct. Biol. Cryst. Commun. 2011, 67:1492-1497.
96. Mallya M., et al. Small molecules block the polymerization of Z α1-antitrypsin and increase the clearance of intracellular aggregates. J. Med. Chem. 2007, 50:5357-5363.
97. 1-antitrypsin conformers. PLoS ONE 2012, 7:e36612.
98. Hidvegi T., et al. An autophagy-enhancing drug promotes degradation of mutant α1-antitrypsin Z and reduces hepatic fibrosis. Science 2010, 329:229-232.
99. Pastore N., et al. Autophagy master regulator TFEB induces clearance of toxic SERPINA1/α-1-antitrypsin polymers. Autophagy 2013, 9:1094-1096.
100. Kaushal S., et al. Rapamycin reduces intrahepatic α-1-antitrypsin mutant Z protein polymers and liver injury in a mouse model. Exp. Biol. Med. (Maywood) 2010, 235:700-709.
101. Pan S., et al. Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency. Hepatology 2009, 50:275-281.
102. Bouchecareilh M., et al. Histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA)-mediated correction of α1-antitrypsin deficiency. J. Biol. Chem. 2012, 287:38265-38278.
103. Somers A., et al. Generation of transgene-free lung disease-specific human induced pluripotent stem cells using a single excisable lentiviral stem cell cassette. Stem Cells 2010, 28:1728-1740.
104. Greene C.M., et al. Anti-apoptotic effects of Z α1-antitrypsin in human bronchial epithelial cells. Eur. Respir. J. 2010, 35:1155-1163.
105. Stockley R.A., et al. Ongoing research in Europe: Alpha One International Registry (AIR) objectives and development. Eur. Respir. J. 2007, 29:582-586.
106. 1-antitrypsin deficiency. Chest 2000, 118:843-848.
107. American Thoracic Society and European Respiratory Society American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with α-1 antitrypsin deficiency. Am. J. Respir. Crit. Care Med. 2003, 168:818-900.
108. Saibil H.R., et al. Heritable yeast prions have a highly organized three-dimensional architecture with interfiber structures. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:14906-14911.
109. Waudby C.A., et al. Rapid distinction of intracellular and extracellular proteins using NMR diffusion measurements. J. Am. Chem. Soc. 2012, 134:11312-11315.
110. Collinge J., Clarke A.R. A general model of prion strains and their pathogenicity. Science 2007, 318:930-936.
111. Fitzpatrick A.W., et al. Atomic structure and hierarchical assembly of a cross-β amyloid fibril. Proc. Natl. Acad. Sci. U.S.A. 2013, 110:5468-5473.
112. Carnall J.M., et al. Mechanosensitive self-replication driven by self-organization. Science 2010, 327:1502-1506.
113. Mannige R.V., et al. A universal trend among proteomes indicates an oily last common ancestor. PLoS Comput. Biol. 2012, 8:e1002839.
114. Ward J.J., et al. Prediction and functional analysis of native disorder in proteins from the 3 kingdoms of life. J. Mol. Biol. 2004, 337:634-645.
115. 52Phe deleted) forms loop-sheet polymers in vivo: evidence for the C sheet mechanism of polymerisation. J. Biol. Chem. 1995, 270:16864-16870.
116. 1-antitrypsin deficiency variant, Mnichinan. Am. J. Hum. Genet. 1990, 46:602-612.
117. 53→Phe); further evidence for intracellular loop-sheet polymerisation. J. Biol. Chem. 1993, 268:15333-15335.
118. brescia α1-antitrypsin allele. Hum. Mutat. 2009, 30:E771-E781.
119. 1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization. PLoS ONE 2012, 7:e38405.
120. 1-antitrypsin and liver cirrhosis. J. Clin. Invest. 1999, 103:999-1006.
121. 1-antitrypsin alleles PI Mwurzburg (Pro369Ser), Mheerlen (Pro369Leu), and Q0 Lisbon (Thr68Ile). Eur. J. Hum. Genet. 1999, 7:321-331.
122. Gadek J.E., et al. Replacement therapy of α-1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. J. Clin. Invest. 1981, 68:1158-1165.
123. 1-antitrypsin. Nat. Struct. Biol. 1996, 3:676-681.
124. 1-antitrypsin is in the canonical inhibitory conformation. J. Mol. Biol. 1998, 275:419-425.
125. Johnson D.J., et al. Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation. EMBO J. 2006, 25:2029-2037.
126. Haq I., et al. Reactive centre loop mutants of α-1-antitrypsin reveal position-specific effects on intermediate formation along the polymerization pathway. Biosci. Rep. 2013, 33:499-511.