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Alpha b-crystallin as a therapy for inflammation

A technology for crystal proteins and inflammatory diseases, which can be used in antibody medical components, peptide/protein components, medical preparations containing active ingredients, etc., and can solve disputes and other issues

Inactive Publication Date: 2009-11-04
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Immunosuppressants such as mycophenolate mofetil and cyclophosphamide have been used in many patients with severe progressive MS, but are controversial

Method used

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  • Alpha b-crystallin as a therapy for inflammation
  • Alpha b-crystallin as a therapy for inflammation
  • Alpha b-crystallin as a therapy for inflammation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 2

[0188] Mitogen-activated protein kinases called MAP kinases are key players in inflammation. P38MapK and the extracellular signal-regulated kinase ERK are critical in the inflammatory response and have been shown to play a role in myocardial infarction, stroke and peripheral arterial ischemia, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis plays a key role. For example, interferon gamma is regulated by p38MapK and ERK signaling, see Figure 10 .

[0189] We demonstrate that the absence of aBC affects the p38MapK and ERK pathways in brain and peripheral macrophages and lymphocytes. Administration of aBC can affect inflammatory neurological diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and stroke by affecting these pathways in the central nervous system.

[0190] like figure 1 As shown, administration of aBC reduced the production of pro-inflammatory cytokines by peripheral blood lymphocytes. like f...

Embodiment 3

[0194] Treatment of autoimmune arthritis in an animal model of collagen-induced arthritis with aB crystallin.

[0195] In addition to studies in the EAE model of MS, this paper demonstrates that aBC can treat established autoimmune arthritis in a rodent RA model. In these studies, induction with type II bovine collagen emulsified in Freund's complete adjuvant and boosted 21 days later with type II bovine collagen in Freund's incomplete adjuvant produced collagen-induced arthritis in mice.

[0196] After the mice developed clinical arthritis, the arthritic mice were randomly divided into groups to receive treatment with aBC ((10 μg, every other day), myosin (10 μg) or PBS (saline control) every other day. Treatment with aBC had produced arthritis Compared with mice treated with myosin or PBS control, the severity of arthritis was significantly reduced (P Figure 11). Mice were then sacrificed to collect joints, fixed, decalcified, paraffin-embedded, sectioned, stained with tolu...

Embodiment 4

[0198] αBC protects hippocampal neurons from Aβ-induced apoptosis.

[0199] The hippocampal tissues of E15-16 suckling mice were harvested, collected in ice-cold calcium and magnesium-free HBSS solution, and then digested with 0.05% trypsin at 37°C for 5 minutes. Cells were dissociated and resuspended in serum-free DMEM / F12. Tissue culture wells (Costar 96-well A / 2 plate, 0.16cm 2 / well) was pre-coated with 25 μL / well of poly-L-lysine (10 μg / ml in phosphate-buffered saline, Sigma) at 37° C. for 1 hour. After aspirating the liquid, add 45 μl cell suspension to each well (2000 neurons / well; 12,500 cells / cm 2 ) and containing N 2 5 [mu]l of serum-free DMEM / F12 broth supplemented with recombinant BDNF (R&D Systems, Minneapolis, MN). Culture conditions, including low cell density and serum-free DMED, were similar to those used to culture primary hippocampal cells reported by Lindholm et al. (1996). After 6-7 days of in vitro culture (DIV), hippocampal neurons were exposed to c...

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Abstract

The invention provides methods for treating inflammatory diseases by administering to the subject an effective amount of an agent that provides alpha B-crystallin activity, where the dose is effective to suppress or prevent initiation, progression, or relapses of disease, including the progression of established disease. In some embodiments, the methods of the invention comprise administering to a subject having a pre-existing inflammatory disease condition, an effective amount of alpha B-crystallin protein, to suppress or prevent relapses of the disease.

Description

Background of the invention [0001] αB crystallin (αBC), a member of the small heat shock protein family, is found in high abundance in the lens of the eye. Together with αA, β and γ-crystallin, αBC forms the main water-soluble structural protein of the vertebrate eye lens, which produces the required refractive index. Studies have suggested that α-crystallin is also involved in the role of molecular chaperones, which can bind to unfolded denatured proteins to inhibit the non-specific aggregation of the lens and maintain its transparency. Interestingly, nude mice knocked out of the αBC gene had normal lenses, suggesting that this crystallin is not required for the development of clear lenses. In addition to the lens of the eye, αBC levels are also high in adult cardiac and skeletal muscle, while expression is low in kidney, lung, central nervous system (CNS) glia, liver, and developing heart and somites. [0002] αBC expression is associated with several pathological conditio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/00A61K38/17
Inventor L·斯坦曼S·S·奥斯曼W·H·鲁滨逊
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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