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Neuroprotective molecules and methods of treating neurological disorders and inducing stress granules

  • US 9,676,810 B2
  • Filed: 07/08/2011
  • Issued: 06/13/2017
  • Est. Priority Date: 07/08/2010
  • Status: Active Grant
First Claim
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1. A neuroprotective molecule consisting of:

  • (i) a sequence of 25-35 contiguous nucleotides that is identical to a contiguous sequence between nucleotide 1 and nucleotide 50 of a mature human transfer ribonucleic acid (tRNA) having a sequence selected from the group consisting of SEQ ID NOs;

    32, 37, 40-46 and 48-55, wherein a first nucleotide of the 25-35 contiguous nucleotides corresponds to nucleotide position 1 of the mature human tRNA sequence;

    at least part of the sequence of 25-35 contiguous nucleotides forms a D-loop stem structure; and

    at least part of the sequence of 25-35 contiguous nucleotides binds to YB-1;

    (ii) optionally a 5′

    -monophosphate, one or more modified nucleotides, and/or one or more modifications in a phosphate backbone in the nucleotide(s) in (i) of the neuroprotective molecule; and

    (ii) optionally a 5′

    -protective group and/or a 3-′

    protective group;

    wherein at least four contiguous nucleotides in (i) of the neuroprotective molecule at the 5′

    end are guanosine deoxyribonucleotides;

    the neuroprotective molecule binds YB-1; and

    the neuroprotective molecule is capable of decreasing protein translation in a rabbit reticulocyte assay.

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