排序方式: 共有14条查询结果,搜索用时 31 毫秒
1.
2.
V. Bellotti P. Mangione M. Stoppini 《Cellular and molecular life sciences : CMLS》1999,55(6-7):977-991
The physiological metabolism of proteins guarantees that different cellular compartments contain the appropriate concentration
of proteins to perform their biological functions and, after a variable period of wear and tear, mediates their natural catabolism.
The equilibrium between protein synthesis and catabolism ensures an effective turnover, but hereditary or acquired abnormalities
of protein structure can provoke a premature loss of biological function, an accelerated catabolism and diseases caused by
the loss of an irreplaceable function. In certain proteins, abnormal structure and metabolism are associated with a strong
tendency to self-aggregation into a polymeric fibrillar structure, and in these cases the disease is not principally caused
by the loss of an irreplaceable function but by the action of this new biological entity. Amyloid fibrils are an apparently
inert, insoluble, mainly extracellular protein polymer that kills the cell without tissue necrosis but by activation of the
apoptotic mechanism. We analyzed the data reported so far on the structural and functional properties of four prototypic proteins
with well-known biological functions (lysozyme, transthyretin, β2-microglobulin and apolipoprotein AI) that are able to create
amyloid fibrils under certain conditions, with the perspective of evaluating whether the achievement of biological function
favors or inhibits the process of fibril formation. Furthermore, studying the biological functions carried out by amyloid
fibrils reveals new types of protein-protein interactions in the transmission of messages to cells and may provide new ideas
for effective therapeutic strategies.
Received 9 November 1998; received after revision 15 January 1999; accepted 15 January 1999 相似文献
3.
Pepys MB Hirschfield GM Tennent GA Gallimore JR Kahan MC Bellotti V Hawkins PN Myers RM Smith MD Polara A Cobb AJ Ley SV Aquilina JA Robinson CV Sharif I Gray GA Sabin CA Jenvey MC Kolstoe SE Thompson D Wood SP 《Nature》2006,440(7088):1217-1221
Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury. 相似文献
4.
Pang ZP Yang N Vierbuchen T Ostermeier A Fuentes DR Yang TQ Citri A Sebastiano V Marro S Südhof TC Wernig M 《Nature》2011,476(7359):220-223
5.
Pluripotent stem cells induced from adult neural stem cells by reprogramming with two factors 总被引:3,自引:0,他引:3
Kim JB Zaehres H Wu G Gentile L Ko K Sebastiano V Araúzo-Bravo MJ Ruau D Han DW Zenke M Schöler HR 《Nature》2008,454(7204):646-650
6.
A novel AMPK-dependent FoxO3A-SIRT3 intramitochondrial complex sensing glucose levels 总被引:1,自引:1,他引:0
Alessia Peserico Fulvio Chiacchiera Valentina Grossi Antonio Matrone Dominga Latorre Marta Simonatto Aurora Fusella James G. Ryall Lydia W. S. Finley Marcia C. Haigis Gaetano Villani Pier Lorenzo Puri Vittorio Sartorelli Cristiano Simone 《Cellular and molecular life sciences : CMLS》2013,70(11):2015-2029
7.
Bodin K Ellmerich S Kahan MC Tennent GA Loesch A Gilbertson JA Hutchinson WL Mangione PP Gallimore JR Millar DJ Minogue S Dhillon AP Taylor GW Bradwell AR Petrie A Gillmore JD Bellotti V Botto M Hawkins PN Pepys MB 《Nature》2010,468(7320):93-97
Accumulation of amyloid fibrils in the viscera and connective tissues causes systemic amyloidosis, which is responsible for about one in a thousand deaths in developed countries. Localized amyloid can also have serious consequences; for example, cerebral amyloid angiopathy is an important cause of haemorrhagic stroke. The clinical presentations of amyloidosis are extremely diverse and the diagnosis is rarely made before significant organ damage is present. There is therefore a major unmet need for therapy that safely promotes the clearance of established amyloid deposits. Over 20 different amyloid fibril proteins are responsible for different forms of clinically significant amyloidosis and treatments that substantially reduce the abundance of the respective amyloid fibril precursor proteins can arrest amyloid accumulation. Unfortunately, control of fibril-protein production is not possible in some forms of amyloidosis and in others it is often slow and hazardous. There is no therapy that directly targets amyloid deposits for enhanced clearance. However, all amyloid deposits contain the normal, non-fibrillar plasma glycoprotein, serum amyloid P component (SAP). Here we show that administration of anti-human-SAP antibodies to mice with amyloid deposits containing human SAP triggers a potent, complement-dependent, macrophage-derived giant cell reaction that swiftly removes massive visceral amyloid deposits without adverse effects. Anti-SAP-antibody treatment is clinically feasible because circulating human SAP can be depleted in patients by the bis-d-proline compound CPHPC, thereby enabling injected anti-SAP antibodies to reach residual SAP in the amyloid deposits. The unprecedented capacity of this novel combined therapy to eliminate amyloid deposits should be applicable to all forms of systemic and local amyloidosis. 相似文献
8.
9.
10.