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 displaying signs and/or symptoms of Alzheimer's disease; and
ii) a composition comprising a dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic selenium; and
b) administering said composition to said subject under conditions such that brain 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 brain specific expression occurs in the cerebral cortex of said subject.
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 encoding a protease.
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 subject displaying signs and/or symptoms of Alzheimer's disease has been diagnosed as having Alzheimer's disease.
10 . The method of claim 1 , wherein reducing expression of said gene encoding a protein associated with processing amyloid precursor protein reduces amyloid β plaque levels in the brain of said subject.
11 . The method of claim 1 , wherein said dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic 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.
12 . The method of claim 1 , wherein said dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic selenium is administered to said subject in such a way so as to provide 200 μg of selenium to said subject each day.
13 . A method of inhibiting the expression of a gene encoding a protein involved in the generation of amyloid β-peptide in a subject comprising:
a) providing:
i) a subject, wherein said subject is suspected of or identified as having elevated levels of amyloid β-peptide compared to a normal, healthy subject; and
ii) a composition comprising a dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic selenium; and
b) administering said composition to said subject suspected of or identified as having elevated levels of amyloid β-peptide under conditions such that said expression of a gene encoding a protein involved in the generation of amyloid β-peptide is reduced in said subject.
14 . The method of claim 13 , wherein said gene encoding a protein associated with the generation of amyloid β-peptide is selected from the group consisting of cathepsin B, cathepsin D, cathepsin Z, and cathepsin O, presenilin-1, presenilin-2, and nicastrin.
15 . The method of claim 13 , wherein said gene encoding a protein associated with the generation of amyloid β-peptide is calsenilin.
16 . The method of claim 13 , wherein reducing expression of said gene encoding a protein involved in the generation of amyloid β-peptide reduces the amount of amyloid β plaques in the brain of said subject.
17 . The method of claim 13 , wherein said subject suspected of or identified as having elevated levels of amyloid β-peptide compared to a normal, healthy subject is a subject identified as having Alzheimer's disease.
18 . The method of claim 13 , wherein administering a composition comprising a dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic selenium reduces the processing of amyloid precursor protein (APP) to amyloid β-peptide in said subject.”
19 . 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 a dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic selenium; and
b) administering said composition to said subject under conditions such that the expression of Presenilin 1 is reduced in said subject; and
c) detecting said expression of Presenilin 1.
20 . The method of claim 19 , wherein said dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic 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.
21 . The method of claim 19 , wherein said dried, nonviable selenium-enriched yeast wherein the total selenium content of said yeast comprises two percent or less inorganic selenium is administered to said subject in such a way so as to provide 200 μg of selenium to said subject each day.
22 . The method of claim 19 , wherein said detecting said expression of presenilin 1 comprises use of an oligonucleotide probe.
23 . The method of claim 19 , wherein said detecting said expression of presenilin 1 comprises use of polymerase chain reaction (PCR).
24 . The method of claim 23 , wherein said PCR comprises reverse transcriptase (RT) PCR.
25 . The method of claim 18 , wherein the expression of a complement gene is reduced in said subject.
26 . The method of claim 25 , wherein said complement gene is selected from the group consisting of complement component 1, q subcomponent binding protein (C1qbp), complement component 1, q subcomponent, alpha polypeptide (C1qa), complement component 1, q subcomponent, beta polypeptide, (C1qbp), complement component 1, q subcomponent, gamma polypeptide (C1qg), and (complement component 1, r subcomponent, C1r).
27 . The method of claim 26 , wherein said complement gene is complement component 1, q subcomponent binding protein (C1qbp).
28 . The method of claim 25 , wherein the expression of nicastrin and calsenilin are reduced in said subject.