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 of reducing age associated expression of a gene encoding a protein associated with neurodegenerative disease 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 age associated expression of a gene encoding a protein associated with neurodegenerative disease is altered in said subject.
2 . The method of claim 1 , wherein said gene encoding a protein associated with neurodegenerative disease is a complement gene.
3 . The method of claim 2 , wherein said age associated expression of said complement gene is reduced in said subject.
4 . The method of claim 3 , wherein said complement gene is selected from the group consisting of C1q, C1q alpha, C1q beta, C1q gamma, and C1qr.
5 . The method of claim 2 , wherein said age associated expression of said complement gene is enhanced in said subject.
6 . The method of claim 5 , wherein said complement gene is CD59-alpha.
7 . The method of claim 1 , wherein said gene encoding a protein associated with neurodegenerative disease 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 1 , wherein said gene encoding a protein associated with neurodegenerative disease is a presenilin gene.
10 . The method of claim 9 , wherein said presenilin gene is selected from the group consisting of presenilin-1 and presenilin-2.
11 . The method of claim 1 , wherein said gene encoding a protein associated with neurodegenerative disease is calsenilin.
12 . The method of claim 1 , wherein said gene encoding a protein associated with neurodegenerative disease is prohibitin.
13 . The method of claim 1 , wherein said gene encoding a protein associated with neurodegenerative disease is selected from the group consisting of Apbb1/Fe65, Aplp1 and Apba1.
14 . The method of claim 1 , wherein said composition comprising selenium is administered to said subject so as to provide 200 μg of selenium to said subject each day.
15 . The method of claim 1 , wherein said composition comprising selenium is administered to said subject so as to provide between 25 and 400 μg of selenium to said subject each day.
16 . The method of claim 1 , wherein said composition comprising selenium comprises SEL-PLEX.
17 . The method of claim 16 , wherein said composition comprising SEL-PLEX comprises one or more other forms of selenium.
18 . The method of claim 17 , wherein said one or more other forms of selenium comprises sodium-selenite.
19 . The method of claim 1 , wherein said composition comprising selenium is co-administered with an Alzheimer's therapeutic.
20 . The method of claim 19 , wherein said Alzheimer's therapeutic is selected from the group consisting of a NMDA antagonist, an AChE inhibitor, and a metal chelator.
21 . The method of claim 20 , wherein said NMDA antagonist is memantine.
22 . The method of claim 20 ,wherein said AChE inhibitor is tacrine, donepezil, rivastigmine, or galantamine.
23 . The method of claim 20 , wherein said metal chelator is clioquinol.
24 . The method of claim 1 , wherein administering said composition comprising selenium inhibits the onset of Alzheimer's disease signs and symptoms in said subject.
25 . The method of claim 1 , wherein said composition comprising SEL-PLEX is co-administered with an antioxidant.
26 . The method of claim 25 , 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
27 . The method of claim 1 , wherein said composition comprising SEL-PLEX is administered to said subject as a prophylactic or therapeutic treatment for neurodegenerative disease.
28 . The method of claim 12 , wherein reducing prohibitin gene expression is associated with a reduction of mictochondrial stress.