Neurotrophic components of the adnf i complex
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.
Claims
exact text as granted — not AI-modified1 - 17 . (canceled)
18 . A method for reducing neuronal cell death, the method comprising contacting the neuronal cells with an Activity Dependent Neurotrophic Factor I complex (ADNF I) polypeptide in an amount sufficient to prevent neuronal cell death, wherein the ADNF I complex polypeptide comprises an amino acid sequence or a fragment thereof selected from the group consisting of:
WSDVGVSSGSAPDAFK
(SEQ ID NO:1)
NNSTTYAPISANVSTALGSTAALPTAAGPV
(SEQ ID NO:2)
NFLTSHYSAANSVVGGTNPGK
(SEQ ID NO:3)
NPSGTDWLNTNNQANPFN
(SEQ ID NO:4)
LVPLTPINR
(SEQ ID NO:5)
VLQAVXGADSNVAFQGKVIYRSESSGTSELLTR
(SEQ ID NO:6)
GPTADITLTK
(SEQ ID NO:7)
GTPTGXGPLIQ
(SEQ ID NO:8)
VDPASGYPIVGYT
(SEQ ID NO:9)
PSGTDWLNT
(SEQ ID NO:10)
and
SESSGTSELLTR.
(SEQ ID NO:11)
19 . The method of claim 18 , wherein the ADNF I complex polypeptide comprises at least one D-amino acid.
20 . The method of claim 18 , wherein the ADNF I complex polypeptide comprises all D-amino acids.
21 . The method of claim 18 , wherein the neuronal cells are selected from the group consisting of spinal cord neurons, hippocampal neurons, cerebral cortical neurons and cholinergic neurons.
22 . The method of claim 18 , wherein the neuronal cell death is in a patient infected with immunodeficiency virus.
23 . The method of claim 22 , wherein the immunodeficiency virus is a human immunodeficiency virus.
24 . The method of claim 18 , wherein the neuronal cell death is associated with excito-toxicity induced by N-methyl-D-aspartate stimulation.
25 . The method of claim 18 , wherein the neuronal cell death is induced by the beta-amyloid peptide in a patient afflicted with Alzheimer's disease.
26 . The method of claim 18 , wherein the neuronal cell death is induced by cholinergic blockade in a patient afflicted with Alzheimer's disease, the cholinergic blockade resulting in learning impairment.
27 . A method for treating oxidative stress in a patient, the method comprising administering to the patient an Activity Dependent Neurotrophic Factor I complex (ADNF I) polypeptide in an amount sufficient to reduce oxidative stress, wherein the ADNF I complex polypeptide comprises an amino acid sequence or a fragment thereof selected from the group consisting of:
WSDVGVSSGSAPDAFK
(SEQ ID NO:1)
NNSTTYAPISANVSTALGSTAALPTAAGPV
(SEQ ID NO:2)
NFLTSHYSAANSVVGGTNPGK
(SEQ ID NO:3)
NPSGTDWLNTNNQANPFN
(SEQ ID NO:4)
LVPLTPINR
(SEQ ID NO:5)
VLQAVXGADSNVAFQGKVIYRSESSGTSELLTR
(SEQ ID NO:6)
GPTADITLTK
(SEQ ID NO:7)
GTPTGXGPLIQ
(SEQ ID NO:8)
VDPASGYPIVGYT
(SEQ ID NO:9)
PSGTDWLNT
(SEQ ID NO:10)
and
SESSGTSELLTR.
(SEQ ID NO:11)
28 . The method of claim 27 , wherein the ADNF I complex polypeptide comprises at least one D-amino acid.
29 . The method of claim 27 , wherein the ADNF I complex polypeptide comprises all D-amino acids.
30 . 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 an ADNF I complex polypeptide in an amount sufficient to reduce the condition associated with fetal alcohol syndrome, wherein the ADNF I complex polypeptide comprises an amino acid sequence or a fragment thereof selected from the group consisting of:
WSDVGVSSGSAPDAFK
(SEQ ID NO:1)
NNSTTYAPISANVSTALGSTAALPTAAGPV
(SEQ ID NO:2)
NFLTSHYSAANSVVGGTNPGK
(SEQ ID NO:3)
NPSGTDWLNTNNQANPFN
(SEQ ID NO:4)
LVPLTPINR
(SEQ ID NO:5)
VLQAVXGADSNVAFQGKVIYRSESSGTSELLTR
(SEQ ID NO:6)
GPTADITLTK
(SEQ ID NO:7)
GTPTGXGPLIQ
(SEQ ID NO:8)
VDPASGYPIVGYT
(SEQ ID NO:9)
PSGTDWLNT
(SEQ ID NO:10)
and
SESSGTSELLTR.
(SEQ ID NO:11)
31 . The method of claim 30 , wherein the condition is selected from the group consisting of: a decreased body weight of a subject; a decreased brain weight of the subject; a decreased level of VIP mRNA of a subject; and death of a subject in utero.
32 . The method of claim 30 , wherein the ADNF I complex polypeptide comprises at least one D-amino acid.
33 . The method of claim 30 , wherein the ADNF I complex polypeptide comprises all D-amino acids.
34 - 45 . (canceled)
46 . A method for improving learning and/or memory in a subject, the method comprising the step of administering prenatally to the subject an Activity Dependent Neurotrophic Factor I complex (ADNF I) polypeptide in an amount sufficient to improve postnatal learning and/or memory of the subject, wherein the ADNF I complex polypeptide comprises an amino acid sequence or a fragment thereof selected from the group consisting of:
WSDVGVSSGSAPDAFK
(SEQ ID NO:1)
NNSTTYAPISANVSTALGSTAALPTAAGPV
(SEQ ID NO:2)
NFLTSHYSAANSVVGGTNPGK
(SEQ ID NO:3)
NPSGTDWLNTNNQANPFN
(SEQ ID NO:4)
LVPLTPINR
(SEQ ID NO:5)
VLQAVXGADSNVAFQGKVIYRSESSGTSELLTR
(SEQ ID NO:6)
GPTADITLTK
(SEQ ID NO:7)
GTPTGXGPLIQ
(SEQ ID NO:8)
VDPASGYPIVGYT
(SEQ ID NO:9)
PSGTDWLNT
(SEQ ID NO:10)
and
SESSGTSELLTR.
(SEQ ID NO:11)
47 . The method of claim 46 , wherein the subject has normal mental capacity.
48 . The method of claim 46 , wherein the subject has mental retardation, a family history of mental retardation, Down's syndrome, or a mother who is at least 35 years of age when pregnant with the subject.
49 . The method of claim 48 , wherein mental retardation is not caused by consumption of alcohol by the subject's mother during pregnancy.
50 . The method of claim 46 , wherein the ADNF I complex polypeptide is administered around the time of neural tube development and/or closure of the neural tube.
51 . The method of claim 46 , wherein the ADNF I complex polypeptide is intraperitoneally administered to the mother during pregnancy.
52 . The method of claim 46 , wherein the ADNF I complex polypeptide is orally or nasally administered to the mother during pregnancy.
53 . The method of claim 46 , wherein the ADNF I complex polypeptide is encoded by a nucleic acid which is administered to the subject.
54 . The method of claim 46 , wherein the ADNF I complex polypeptide comprises at least one D-amino acid.
55 . The method of claim 46 , wherein the ADNF I complex polypeptide comprises all D-amino acids.Join the waitlist — get patent alerts
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