Neurotrophic components of the adnf i complex

a neurotrophic factor and complex technology, applied in the field of activity dependent neurotrophic factor complexes, can solve the problems of severe debilitating conditions, and achieve the effects of enhancing the activity of components i, blocking the survival-promoting activity, and enhancing the survival-promoting activity

Inactive Publication Date: 2009-10-01
THE GOVERMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE +2
View PDF15 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]The present invention is also based upon a surprising discovery that new ADNF I complex polypeptides are effective for reducing neuronal cell death, for reducing oxidative stress, for reducing condition(s) associated with fetal alcohol syndrome in a subject, for enhancing learning and memory, both pre- and post-natally, and for other conditions. The ADNF I complex polypeptides contain active sites and provide neuroprotective and growth-promoting functions. These ADNF I complex polypeptides are from subunits of ADNF I and / or accessory molecules of ADNF I, which co-isolate with ADNF I from conditioned medium of VIP-stimulated astrocyte cultures. Antiserum to these polypeptides blocks the action of ADNF I and ADNF I complex polypeptides.
[0021]In yet another aspect, the present invention provides a method for reducing a condition associated with fetal alcohol syndrome in a subject who is exposed to alcohol in utero, the method comprising administering to the subject at least one ADNF I complex polypeptide described above in an amount sufficient to reduce a condition associated with fetal alcohol syndrome.
[0023]In another aspect, the present invention provides a method for improving learning and / or memory in a subject, the method comprising the step of administering postnatally to the subject at least one ADNF I complex polypeptide described above in an amount sufficient to improve postnatal learning and / or memory of the subject.
[0025]In another embodiment, the polypeptide improves short term or reference memory.
[0026]In another aspect, the present invention provides a method for improving learning and / or memory in a subject, the method comprising the step of administering prenatally to the subject at least one ADNF I complex polypeptide described above in an amount sufficient to improve prenatal learning and / or memory of the subject.

Problems solved by technology

These diseases and conditions are severely debilitating and have a lifelong impact on individuals diagnosed with such diseases and conditions.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Neurotrophic components of the adnf i complex
  • Neurotrophic components of the adnf i complex
  • Neurotrophic components of the adnf i complex

Examples

Experimental program
Comparison scheme
Effect test

examples

[0220]The following examples are offered to illustrate, but not to limit the claimed invention.

example i

Demonstration of Additional Subunits or Accessory Components of ADNF I Complex

[0221]Evidence is presented that purified ADNF I, when analyzed under acidic conditions or when treated with a protease inhibitor cocktail (see Example III), exhibited a complex dose response for survival-promoting activity that indicates the existence of labile and novel components that were not previously identified. These data are consistent with the existence of labile components of the ADNF I complex that are only apparent when a serine protease inhibitor is present or when the pH is lowered to 4.5.

[0222]ADNF I was isolated as previously described (see, e.g., Brenneman & Gozes, J. Clin. Invest. 97:2299-2307 (1996)) and then desalted and stored in 10 mM phosphate buffer (pH 4.5). The purified ADNF I was diluted 1:3 with water and analyzed on eCAP / SDS capillary electrophoresis (CE). The running and sample buffers for these analyses were components of the eCAP / SDS kit (Beckmann Instruments). Electrophore...

example ii

Demonstration of Tryptic Digest Peptides from ADNF I Complex and their Neuroprotective Activity in CNS Cultures

[0224]Digest peptides were obtained after treatment of purified ADNF I with trypsin as previously described (Williams & Stone, Techniques in Protein Chemistry VI. pp 79-90 (1997)). As shown in FIG. 3, the peptides were separated by reverse phase HPLC. The peptide identified for each of the peaks is given as the first three amino acids of the peptide. Aliquots of the isolated peptides were sequenced by Edman degradation or tested for survival-promoting activity in TTX-treated cerebral cortical cultures. As shown in FIG. 4, three digest peptide fractions exhibited survival-promoting activity in vitro. The active peptides were:

[0225]1. NNSTTYAPISANVSTALGSTAALPTAAGPV (SEQ ID NO:2) (retention time: 62 min) Abrev.: NNST

[0226]2. GPTADITLTK (SEQ ID NO:7) (retention time: 43 min) Abrev.: GPT

[0227]3. NPSGTDWLNTNNQANPFN (SEQ ID NO:4) (retention time: 71 min) Abrev. PSG

[0228]One additi...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
constant voltageaaaaaaaaaa
diameteraaaaaaaaaa
Login to view more

Abstract

This invention relates to Activity Dependent Neurotrophic Factor I complex (ADNF I complex) and polypeptides of this complex, which produce their neurotrophic effects through multiple proteases intrinsic to the ADNF I complex. The invention also relates to pharmaceutical compositions comprising ADNF I complex polypeptides, as well as methods for reducing neuronal cell death in vitro and in vivo, methods for treating oxidative stress in a patient, methods for reducing a condition associated with fetal alcohol syndrome in a subject, and methods of enhancing learning and memory both pre- and post-natally, all of which methods use the ADNF I complex polypeptides of the invention.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. National Phase application Ser. No. 10 / 489,515, filed Oct. 14, 2004, which is a National Phase Application under 35 U.S.C. § 371 of Application No. PCT / US2002 / 29146, filed Sep. 12, 2002, which claims priority to U.S. Provisional Application No. 60 / 322,760 filed Sep. 12, 2001 and U.S. Provisional Application No. 60 / 371,961, filed Apr. 10, 2001. All of these applications are incorporated herein by reference.[0002]This application is related to U.S. Ser. No. 07 / 871,973 filed Apr. 22, 1992, now U.S. Pat. No. 5,767,240; U.S. Ser. No. 08 / 342,297, filed Oct. 17, 1994 (published as WO96 / 11948), now U.S. Pat. No. 6,174,862; U.S. Ser. No. 60 / 037,404, filed Feb. 7, 1997 (published as WO98 / 35042); U.S. Ser. No. 09 / 187,330, filed Nov. 11, 1998 (published as WO00 / 27875); U.S. Ser. No. 09 / 267,511, filed Mar. 12, 1999 (published as WO00 / 53217); U.S. Ser. No. 60 / 149,956, filed Aug. 18, 1999 (published as WO01 / 12...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/17C12N5/00A61K38/10A61K38/08A61P25/28A61P25/32A61P15/00A61P25/00A61K38/00C07K14/475C07K14/48
CPCC07K14/475A61K38/00
Inventor BRENNEMAN DOUGLAS E.CASTELLON RAQUELSPONG CATHERINE Y.HAUSER JANET M.GOZES IIIANA
Owner THE GOVERMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap