Methods and compositions for altering cell function
The present invention relates to compositions and methods for altering cell function. In particular, the present invention provides compositions comprising selenium (e.g., SEL-PLEX) and methods of using the same (e.g., as a therapeutic and/or prophylactic treatment for neurodegenerative disease). Additionally, the present invention demonstrates that specific forms of selenium (e.g., SEL-PLEX) possess the ability to alter expression of genes associated with disease and/or aging while other forms of selenium (e.g., selenomethionine) do not.
1 . A method for treating a subject, comprising:
a) providing:
i) a subject; and
ii) a composition comprising selenium; and
b) administrating said composition to said subject under conditions such that cerebral cortex specific expression of a gene encoding a protein associated with processing amyloid precursor protein is reduced in said subject.
2 . The method of claim 1 , wherein said composition comprising selenium comprises SEL-PLEX.
3 . The method of claim 1 , wherein said gene encoding a protein associated with processing amyloid precursor protein is a presenilin gene.
4 . The method of claim 3 , wherein said presenilin gene is selected from the group consisting of presenilin-1 and presenilin-2.
5 . The method of claim 1 , wherein said gene encoding a protein associated with processing amyloid precursor protein is nicastrin.
6 . The method of claim 1 , wherein said gene encoding a protein associated with processing amyloid precursor protein is calsenilin.
7 . The method of claim 1 , wherein said gene encoding a protein associated with processing amyloid precursor protein is a cathepsin gene.
8 . The method of claim 7 , wherein said cathepsin gene is selected from the group consisting of Cathepsin B, Cathepsin D, Cathepsin Z, and Cathepsin O.
9 . The method of claim 2 , wherein said composition comprising SEL-PLEX comprises one or more other forms of selenium.
10 . The method of claim 9 , wherein said one or more forms of selenium comprises sodium-selenite.
11 . The method of claim 1 , wherein said composition comprising selenium is co-administered with an antioxidant.
12 . The method of claim 11 , wherein said antioxidant is selected from the group consisting of alkylated, diphenylamines, N-alkylated phenylenediamines, phenyl-α-naphthylamine, alkylated phenyl-α-naphthylamine, dimethyl quinolines, trimethyldihydroquinolines, hindered phenolics, alkylated hydroquinones, hydroxylated thiodiphenyl ethers, alkylidenebisphenols, thiopropionates, metallic dithiocarbamates, 1,3,4-dimercaptothiadiazole, an oil soluble copper compound, NAUGALUBE 438, NAUGALUBE 438L, NAUGALUBE 640, NAUGALUBE 635, NAUGALUBE 680, NAUGALUBE AMS, NAUGALUBE APAN, Naugard PANA, NAUGALUBE TMQ, NAUGALUBE 531, NAUGALUBE 431, NAUGALUBE BHT, NAUGALUBE 403, NAUGALUBE 420, ascorbic acid, tocopherols, alpha-tocopherol, a sulfhydryl compound, sodium metabisulfite, N-acetyl-cysteine, lipoic acid, dihydrolipoic acid, resveratrol, lactoferrin, ascorbic acid, ascorbyl palmitate, ascorbyl polypeptide, butylated hydroxytoluene, retinoids, retinol, retinyl palmitate, tocotrienols, ubiquinone, a flavonoid, an isoflavonoid, genistein, diadzein, resveratrol, grape seed, green tea, pine bark, propolis, IRGANOX, Antigene P, SUMILIZER GA-80, beta-carotene, lycopene, vitamin C, vitamin E, and vitamin A.
13 . The method of claim 1 , wherein said composition comprising selenium is co-administered with an Alzheimer's therapeutic.
14 . The method of claim 13 , wherein said Alzheimer's therapeutic is selected from the group consisting of a NMDA antagonist, an AChE inhibitor, and a metal chelator.
15 . The method of claim 14 , wherein said NMDA antagonist is memantine.
16 . The method of claim 14 , wherein said AChE inhibitor is tacrine, donepezil, rivastigmine, or galantamine.
17 . The method of claim 14 , wherein said metal chelator is clioquinol.
18 . The method of claim 17 , wherein said clioquinol chelates zinc and copper.
19 . The method of claim 1 , wherein said subject is selected from the group consisting of a subject at risk of displaying pathology indicative of Alzheimer's disease and a subject having Alzheimer's disease.
20 . The method of claim 1 , wherein reducing expression of said gene encoding a protein associated with processing amyloid precursor protein reduces amyloid β-peptide levels in the cerebral cortex of said subject.
21 . The method of claim 20 , wherein reducing amyloid β-peptide levels reduces formation of Alzheimer's disease plaques in the brain of said subject.
22 . The method of claim 19 , wherein the method for treating is prophylactic.
23 . The method of claim 22 , wherein said prophylactic treatment prevents the onset of signs and symptoms of Alzheimer's disease in said subject.
24 . The method of claim 1 , wherein said composition comprising selenium is administered to said subject in such a way so as to provide 200 μg of selenium to said subject each day.
25 . The method of claim 1 , wherein said composition comprising selenium is administered to said subject in such a way so as to provide between 25 and 400 μg of selenium to said subject each day.
26 . A method of inhibiting the expression of a gene encoding a protein associated with the generation of β-amyloid peptide in a subject comprising:
a) providing:
i) a subject; and
ii) a composition comprising selenium; and
b) administrating said composition to said subject under conditions such that said expression of a gene encoding a protein associated with the generation of β-amyloid peptide is reduced in said subject.
27 . The method of claim 26 , wherein said gene encoding a protein associated with the generation of β-amyloid peptide is selected from the group consisting of cathepsin B, cathepsin D, cathepsin Z, and cathepsin O, presenilin 1, presenilin-2, and nicastrin.
28 . The method of claim 26 , wherein said gene encoding a protein associated with the generation of β-amyloid peptide is calsenilin.
29 . The method of claim 26 , wherein said composition comprising selenium is administered to said subject as a prophylactic or therapeutic treatment for neurodegenerative disease.
30 . The method of claim 26 , wherein said subject is selected from the group consisting of a subject at risk of displaying pathology indicative of Alzheimer's disease and a subject having Alzheimer's disease.
31 . The method of claim 26 , wherein said composition comprising selenium comprises SEL-PLEX.
32 . The method of claim 31 , wherein said composition comprising SEL-PLEX comprises one or more other forms of selenium.
33 . The method of claim 32 , wherein said one or more other forms of selenium comprises sodium-selenite.
34 . The method of claim 25 , wherein said composition comprising selenium is co-administered with an Alzheimer's therapeutic.
35 . The method of claim 34 , wherein said Alzheimer's therapeutic is selected from the group consisting of a NMDA antagonist, an ACHE inhibitor, and a metal chelator.
36 . The method of claim 35 , wherein said NMDA antagonist is memantine.
37 . The method of claim 35 , wherein said ACHE inhibitor is tacrine, donepezil, rivastigmine, or galantamine.
38 . The method of claim 35 , wherein said metal chelator is clioquinol.
39 . The method of claim 38 , wherein said clioquinol chelates zinc and copper
40 . The method of claim 26 , wherein administering said composition comprising selenium inhibits the onset of Alzheimer's disease signs and symptoms in said subject.
41 . The method of claim 26 , wherein said composition comprising selenium is co-administered with an antioxidant.
42 . The method of claim 41 , wherein said antioxidant is selected from the group consisting of alkylated diphenylamines, N-alkylated phenylenediamines, phenyl-α-naphthylamine, alkylated phenyl-α-naphthylamine, dimethyl quinolines, trimethyldihydroquinolines, hindered phenolics, alkylated hydroquinones, hydroxylated thiodiphenyl ethers, alkylidenebisphenols, thiopropionates, metallic dithiocarbamates, 1,3,4-dimercaptothiadiazole, an oil soluble copper compound, NAUGALUBE 438, NAUGALUBE 438L, NAUGALUBE 640, NAUGALUBE 635, NAUGALUBE 680, NAUGALUBE AMS, NAUGALUBE APAN, Naugard PANA, NAUGALUBE TMQ, NAUGALUBE 531, NAUGALUBE 431, NAUGALUBE BHT, NAUGALUBE 403, NAUGALUBE 420, ascorbic acid, tocopherols, alpha-tocopherol, a sulfhydryl compound, sodium metabisulfite, N-acetyl-cysteine, lipoic acid, dihydrolipoic acid, resveratrol, lactoferrin, ascorbic acid, ascorbyl palmitate, ascorbyl polypeptide, butylated hydroxytoluene, retinoids, retinol, retinyl palmitate, tocotrienols, ubiquinone, a flavonoid, an isoflavonoid, genistein, diadzein, resveratrol, grape seed, green tea, pine bark, propolis, IRGANOX, Antigene P, SUMILIZER GA-80, beta-carotene, lycopene, vitamin C, vitamin E, and vitamin A.
43 . A composition comprising SEL-PLEX and an Alzheimer's therapeutic.
44 . The composition of claim 43 , wherein said Alzheimer's therapeutic is selected from the group consisting of a NMDA antagonist, an AChE inhibitor, and a metal chelator.
45 . The composition of claim 44 , wherein said NMDA antagonist is memantine.
46 . The composition of claim 44 , wherein said AChE inhibitor is tacrine, donepezil, rivastigmine, or galantamine.
47 . The composition of claim 44 , wherein said metal chelator is clioquinol.
48 . The composition of claim 43 , further comprising an antioxidant.
49 . The composition of claim 48 , wherein said antioxidant is selected from the group consisting of alkylated diphenylamines, N-alkylated phenylenediamines, phenyl-α-naphthylamine, alkylated phenyl-α-naphthylamine, dimethyl quinolines, trimethyldihydroquinolines, hindered phenolics, alkylated hydroquinones, hydroxylated thiodiphenyl ethers, alkylidenebisphenols, thiopropionates, metallic dithiocarbamates, 1,3,4-dimercaptothiadiazole, an oil soluble copper compound, NAUGALUBE 438, NAUGALUBE 438L, NAUGALUBE 640, NAUGALUBE 635, NAUGALUBE 680, NAUGALUBE AMS, NAUGALUBE APAN, Naugard PANA, NAUGALUBE TMQ, NAUGALUBE 531, NAUGALUBE 431, NAUGALUBE BHT, NAUGALUBE 403, NAUGALUBE 420, ascorbic acid, tocopherols, alpha-tocopherol, a sulfhydryl compound, sodium metabisulfite, N-acetyl-cysteine, lipoic acid, dihydrolipoic acid, resveratrol, lactoferrin, ascorbic acid, ascorbyl palmitate, ascorbyl polypeptide, butylated hydroxytoluene, retinoids, retinol, retinyl palmitate, tocotrienols, ubiquinone, a flavonoid, an isoflavonoid, genistein, diadzein, resveratrol, grape seed, green tea, pine bark, propolis, IRGANOX, Antigene P, SUMILIZER GA-80, beta-carotene, lycopene, vitamin C, vitamin E, and vitamin A.
50 . A method of treating a subject having Alzheimer's disease comprising:
a) providing:
i) a subject with Alzheimer's disease; and
ii) a composition comprising selenium;
b) administrating said composition to said subject under conditions such that the expression of Presenilin 1 is altered in said subject; and
c) detecting said expression of presenilin 1.
51 . The method of claim 50 , wherein said composition comprising selenium comprises SEL-PLEX.
52 . The method of claim 50 , wherein said composition comprising selenium is administered to said subject in such a way so as to provide 200 μg of selenium to said subject each day.
53 . The method of claim 50 , wherein said composition comprising selenium is administered to said subject in such a way so as to provide between 25 and 400 μg of selenium to said subject each day.
54 . The method of claim 50 , wherein said detecting said expression of presenilin 1 comprises use of an oligonucleotide probe.
55 . The method of claim 50 , wherein said detecting said expression of presenilin 1 comprises use of PCR.
56 . The method of claim 55 , wherein said PCR comprises RT-PCR.
57 . A method of altering the expression of a complement gene in the cerebral cortex of a subject comprising:
a) providing:
i) a subject; and
ii) a composition comprising selenium; and
b) administrating said composition to said subject under conditions such that cerebral cortex specific expression of a complement gene is altered in said subject.
58 . The method of claim 57 , wherein said cerebral cortex specific expression of a complement gene is reduced.
59 . The method of claim 58 , wherein said complement gene is selected from the group consisting of C1q, C1q alpha, C1q beta, C1q gamma, and C1qr.
60 . The method of claim 57 , wherein said cerebral cortex specific expression of a complement gene is enhanced.
61 . The method of claim 60 , wherein said complement gene is CD59-alpha.
62 . The method of claim 57 , wherein the expression of a gene selected from the group consisting of Apbb1/Fe65, Aplp 1 and Apba1 is also reduced in the cerebral cortex of said subject.
63 . The method of claim 57 , wherein said composition comprising selenium is administered to said subject in such a way so as to provide 200 μg of selenium to said subject each day.
64 . The method of claim 57 , wherein said composition comprising selenium is administered to said subject in such a way so as to provide between 25 and 400 μg of selenium to said subject each day.
65 . The method of claim 57 , wherein expression of said complement gene is associated with pathology of Alzheimer's disease.