Abstract:
:Conformational or misfolding diseases are a large class of devastating human disorders associated with protein misfolding and aggregation. Most conformational diseases are caused by a combination of genetic and environmental factors, suggesting that spontaneous events can destabilize the protein involved in the pathology or impair the clearance mechanisms of misfolded aggregates. Aging is one of the risk factors associa-ted to these events, and the clinical relevance of conformational disorders is growing dramatically, as they begin to reach epidemic proportions due to increases in mean lifespan. Currently, there are no effective strategies to slow or prevent these diseases. Intrabodies are promising therapeutic agents for the treatment of misfolding diseases, because of their virtually infinite ability to specifically recognize the different conformations of a protein, including pathological isoforms, and because they can be targeted to the potential sites of aggregation (both intra- and extracellular sites). These molecules can work as neutralizing agents against amylo-idogenic proteins by preventing their aggregation, and/or as molecular shunters of intracellular traffic by re-routing the protein from its potential aggregation site. The fast-developing field of recombinant antibody technology provides intrabodies with enhanced binding specificity and stability, together with lower immunogenicity, for use in a clinical setting. This review provides an update on the applications of intrabodies in misfolding diseases, with particular emphasis on an evaluation of their multiple and feasible modes of action.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Cardinale A,Biocca Sdoi
10.2174/156652408783565595subject
Has Abstractpub_date
2008-02-01 00:00:00pages
2-11issue
1eissn
1566-5240issn
1875-5666journal_volume
8pub_type
杂志文章,评审abstract:BACKGROUND:In vertebrates, cilium is crucial for Hedgehog signaling transduction. Forkhead box transcriptional factor FoxF1 is reported to be associated with Sonic Hedgehog (Shh) signaling in many cases. However, the role of FoxF1 in cilium remains unknown. Here, we showed an essential role of FoxF1 in the regulation o...
journal_title:Current molecular medicine
pub_type: 信件
doi:10.2174/1566524019666190405115420
更新日期:2019-01-01 00:00:00
abstract::The currently available knowledge of factors that dictate the development and progression as well as the clinical outcome of colorectal cancers (CRC) is mainly derived from Western countries. Considerable number of publications document different incidence rates and contrasting clinical features of CRC in various grou...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524017666170220094705
更新日期:2017-01-01 00:00:00
abstract::Human genetic data on psychiatric disorders repeatedly demonstrate the involvement of various genes that are associated with neural development and neurogenesis. Neurogenesis is a biological process that is critical in brain development and continues throughout life. Neurogenesis is a multi-step process starting from ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524015666150303002834
更新日期:2015-01-01 00:00:00
abstract::Many autoimmune diseases have genetic associations with the Major Histocompatibility Complex (MHC) class II loci. Susceptibility to Type 1 diabetes mellitus (TIDM) is particularly associated with Human Leucocyte Antigen (HLA) DR3, 4 and associated DQ2, 8 alleles and this is well documented in genetic association studi...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033361591
更新日期:2003-02-01 00:00:00
abstract::After several years of controversy, antibodies (Abs) are now believed to play an important role in the protection against fungal infections. Among them, recent data are strongly supporting the relevance of protective yeast killer toxin-like Abs ("antibiobodies", KT-Abs), which are able to exert a direct microbicidal a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524054022558
更新日期:2005-06-01 00:00:00
abstract:PURPOSE:A small molecular compound, aminooxy-acetic acid (AOA), has been shown to modulate experimental autoimmune encephalomyelitis (EAE). The current study was designed to investigate whether AOA has a similar effect on the development of experimental autoimmune uveitis (EAU) and to further explore underlying mechani...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200211112219
更新日期:2020-01-01 00:00:00
abstract::Germline mutations in the VHL tumour suppressor gene may cause a variety of phenotypes including von Hippel-Lindau (VHL) disease, familial phaeochromocytoma and inherited polycythaemia. VHL disease is a multisystem familial cancer syndrome and is the commonest cause of familial renal cell carcinoma (RCC). VHL disease ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043359827
更新日期:2004-12-01 00:00:00
abstract::Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524014666140128114414
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:The phenotypic severity of β-thalassemia is highly modulated by three genetic modifiers: β-globin (HBB) mutations, co-inheritance of α-thalassemia and polymorphisms in the genes associated with fetal haemoglobin (HbF) production. This study was aimed to evaluate the effect of HbF related polymorphisms mainly...
journal_title:Current molecular medicine
pub_type: 临床试验,杂志文章
doi:10.2174/1566524018666181004121604
更新日期:2018-01-01 00:00:00
abstract::The cell adhesion molecule integrin αvβ3 is an important player in the process of angiogenesis. In the last decades, a series of radiolabeled Arg-Gly-Asp (RGD) peptides targeting integrin αvβ3 has been prepared and optimized for positron emission tomography (PET) and single-photon-emission computed tomography (SPECT) ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131111115347
更新日期:2013-12-01 00:00:00
abstract::The identification of a relevant effector of Ran GTPase (Ran) signaling and its pathways could provide a novel approach to cancer therapeutics. With recent research highlighting the significant relationship between Ran expression and the occurrence and progression of cancer, the development of a small molecule compoun...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411797536688
更新日期:2011-11-01 00:00:00
abstract:BACKGROUND:Macrophages undergo polarization or activation in response to environmental stimuli, an essential process for proper immune response. Meanwhile, excessive activation of macrophages causes autoimmune diseases. It is therefore crucial to prevent over-activation of macrophage in order to maintain the proper imm...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524017666171106114537
更新日期:2017-12-07 00:00:00
abstract::Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attentio...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666201120142953
更新日期:2020-11-20 00:00:00
abstract::Cholesterol is a chameleon bio-molecule in cellular multiplex. It acts as a prelate in almost every cellular compartment with its site specific characteristics viz. regulation of structural veracity and scaffold fluidity of bio-membranes, insulation of electrical transmission in nerves, controlling of genes by making ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200413112030
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND & OBJECTIVE:Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:15 pati...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180207152941
更新日期:2018-03-09 00:00:00
abstract::Genome-wide association studies (GWAS) have become increasingly widely used to determine regions of the genome which may contain loci influencing the risk of neurological disorders. While linkage studies have identified genes that cause a number of Mendelian disorders, linkage analysis is less well suited for the more...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409789105534
更新日期:2009-09-01 00:00:00
abstract::Laboratory and clinical studies have provided evidence of feasibility, safety and efficacy of cell transplantation to treat a wide variety of diseases characterized by tissue and cell dysfunction ranging from diabetes to spinal cord injury. However, major hurdles remain and limit pursuing large clinical trials, includ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407782564381
更新日期:2007-11-01 00:00:00
abstract::Spider venom is a large pharmacological repertoire containing many biologically active peptides, which may have a potent therapeutic implication. Here we investigated a peptide toxin, named lycosin-I, isolated from the venom of the spider Lycosa singoriensis. In contrast to most spider peptide toxins adopting inhibito...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652412803833643
更新日期:2012-12-01 00:00:00
abstract::Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652410790963321
更新日期:2010-03-01 00:00:00
abstract::PTEN (Phosphatase and Tensin homologue deleted on chromosome 10, 10q23.3) is the dominant phosphatase responsible for the dephosphorylation of the 3-position phosphate from the inositol ring of phosphatidylinositol 3,4,5 triphosphate (PIP3), and thereby directly antagonizes the actions mediated by Phosphatidylinositol...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013666131118100542
更新日期:2014-01-01 00:00:00
abstract::Chondroitin sulfate (CS)-glycosaminoglycans (GAGs) are linear, negatively charged polysaccharides attached to CS proteoglycans that make up a major component of biological matrices throughout both central and peripheral tissues. The position of their attached sulfate groups to the CS disaccharide is predicted to influ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200915110707
更新日期:2020-09-15 00:00:00
abstract::Plaque disruption and subsequent thrombus formation play a critical role in the clinical manifestations of atherothrombosis. Vulnerable lesions are characterized by the existence of core rich in lipid, macrophages and tissue factor (TF). Plaque disruption facilitates the interaction between flowing blood with the inne...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652406778018707
更新日期:2006-08-01 00:00:00
abstract::Protein serine/threonine phosphatase-1 (PP-1) is one of the key enzymes responsible for dephosphorylation in vertebrates. Protein dephosphorylation via PP-1 is implicated in many different biological processes including gene expression, cell cycle control, transformation, neuronal transmission, apoptosis, autophage an...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652412803833535
更新日期:2012-12-01 00:00:00
abstract::The central role of glutamate receptors in mediating excitotoxic neuronal death in stroke, epilepsy and trauma has been well established. Glutamate is the major excitatory amino acid transmitter within the CNS and it's signaling is mediated by a number of postsynaptic ionotropic and metabotropic receptors. Although ca...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043479202
更新日期:2004-03-01 00:00:00
abstract::Traditionally regarded as a genetic disease of the cardiac sarcomere, hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease and a significant cause of sudden cardiac death. While the most common etiologies of this phenotypically diverse disease lie in a handful of genes encoding critica...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652412800620020
更新日期:2012-06-01 00:00:00
abstract::Although it has been known for long time that atherosclerosis is associated with lipid deposition, only recently it has been accepted that the plasmatic concentration of cholesterol, especially LDL cholesterol, is a risk factor for atherosclerosis. However, chemically modified LDL, but not native LDL, is able to induc...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524023362177
更新日期:2002-09-01 00:00:00
abstract::Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen, which is the cause of a tick-borne illness occurring in many areas of Africa, Asia, and Europe. CCHF is characterized by a sudden onset of high fever, chills, and severe headache. Other symptoms can include gastrointestinal disorders, such a...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652405774962335
更新日期:2005-12-01 00:00:00
abstract::Peroxisomal proliferator activated receptor gamma (PPARgamma) belongs to the family of nuclear hormone receptors (NHRs), which directly regulate transcription of target genes. The regulatory role of this receptor on lipid metabolism and insulin sensitization is well established. Recently, the overexpression of this re...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407781695765
更新日期:2007-09-01 00:00:00
abstract::Since the discovery almost fifteen years ago that E2F transcription factors are key targets of the retinoblastoma protein (RB), studies of the E2F family have uncovered critical roles in the control of transcription, cell cycle and apoptosis. E2F proteins are encoded by at least eight genes, E2F1 through E2F8. While s...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524010606070739
更新日期:2006-11-01 00:00:00
abstract::The world is aging and we must face the challenges that this brings. One of the reasons for the increasing aging of the world's population is the increase in life expectancy and, since we live longer, it is of paramount importance to live well and to prevent age-associated diseases. In this way, it is crucial to impro...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524018666180907162955
更新日期:2018-01-01 00:00:00