Transposable elements, TDP-43, and neurodegenerative disorders
A method that includes measuring the expression level of at least one transposon in a biological sample from a subject; and determining whether the measured transposon expression exceeds a predetermined level, and if so, administering to the subject a transposon inhibitor in an amount effective to reduce the expression level of a transposon.
1. A method of treatment, comprising
administering to a subject having a TDP-43 associated neurodegenerative disorder a transposon inhibitor in an amount effective to reduce the expression level of a transposon,
wherein the TDP-43 associated neurodegenerative disorder is frontotemporal lobar degeneration (FTLD).
2. The method of claim 1 , further comprising testing for the presence of a TDP-43 associated cytoplasmic inclusion in the subject.
3. The method of claim 1 , wherein the transposon inhibitor is an inhibitor of a protein encoded by a transposon.
4. The method of claim 3 , wherein the protein encoded by the transposon is a transposase; an integrase; a reverse transcriptase; an endonuclease; a protein encoded by gag, pol, or env; an enzyme encoded by ORF1, or an enzyme encoded by ORF2.
5. The method of claim 1 , wherein the transposon inhibitor is an anti-retroviral drug; an inhibitor of reverse transcription; an inhibitor of transposase or integrase activity; an inhibitor of endonuclease activity; a stimulator of DNA repair machinery; a zinc-finger that targets a transposon promoter region; a repressor that inhibits a transposon; an innate antiretroviral resistance factor; a small interfering RNAs (siRNA), short hairpin RNA (shRNA), morpholino, or antisense oligonucleotide directed to a TE transcript; an inhibitor that blocks intercellular transmission of transposon genetic material or protein, or an inhibitor of post-translational processing or proteolysis of a transposon-encoded protein.
6. The method of claim 1 , wherein the transposon is a retrotransposon.
7. The method of claim 6 , wherein the retrotransposon is an LTR-retrotransposon.
8. The method of claim 6 , wherein the retrotransposon is a non-LTR retrotransposon.
9. The method of claim 8 , wherein the non-LTR retrotransposon is a LINE retrotransposon.
10. The method of claim 9 , wherein the LINE retrotransposon is L1.
11. The method of claim 8 , wherein the non-LTR retrotransposon is a SINE retrotransposon.
12. The method of claim 11 , wherein the SINE retrotransposon is an Alu sequence.
13. The method of claim 1 , wherein the transposon is a DNA transposon.
14. The method of claim 1 , wherein the transposon is an autonomous element.
15. The method of claim 1 , wherein the transposon is a nonautonomous element.
16. A method of treatment, comprising:
(a) administering to a subject having a TDP-43 associated neurodegenerative disorder a transposon inhibitor in an amount effective to reduce the expression level of a transposon;
(b) measuring the expression level of at least one transposon in a biological sample from the subject; and
(c) determining whether the measured transposon expression level in the subject exceeds a predetermined level,
wherein the TDP-43 associated neurodegenerative disorder is frontotemporal lobar degeneration (FTLD).
17. The method of claim 16 , wherein the transposon is an L1 LINE retrotransposon.
18. The method of claim 1 , wherein the subject is a human.
19. The method of claim 16 , wherein the subject is a human.