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MOLÉCULES NEUROPROTECTRICES ET MÉTHODES DE TRAITEMENT DE TROUBLES NEUROLOGIQUES ET D'INDUCTION DE GRANULES DE STRESS
专利权人:
EMARA, Mohammed; INC.;THE BRIGHAM AND WOMEN'S HOSPITAL, INC.;ANDERSON, Paul;IVANOV, Pavel;THE BRIGHAM AND WOMENS HOSPITAL
发明人:
ANDERSON, Paul,IVANOV, Pavel,EMARA, Mohammed
申请号:
USUS2011/043400
公开号:
WO2012/006551A2
申请日:
2011.07.08
申请国别(地区):
US
年份:
2012
代理人:
摘要:
Provided herein are neuroprotective molecules containing a sequence of 25-35 contiguous nucleotides that is at least 80% identical to a contiguous sequence between nucleotide 1 and nucleotide 50 of a mature human tRNA and at least four contiguous guanosine-containing nucleotides, where the sequence of 25-35 contiguous nucleotides contains a D-loop stem structure, the at least four contiguous guanosine-containing nucleotides are located at the 5' end of the neuroprotective molecule, and the neuroprotective molecule contains at least one deoxyribonucleotide. Also provided are molecules containing a sequence of 25-35 contiguous nucleotides that is at least 80% identical to a contiguous sequence between nucleotide 1 and nucleotide 50 of a mature human tRNA selected from the group of tRAArg, tRNAAsp, tRNAGln, tRNAGlu, tRNAGly, tRNAHis, tRNAIle, tRNALeu, tRNALys, tRNAMet, tRNAPro, tRNASeC, tRNASer, tRNASup, tRNAThr, tRNATrp, tRNATyr, tRNAVal, tRNAAsn, and tRNAPhe; and at least four contiguous guanosine-containing nucleotides, where the sequence of 25-35 contiguous nucleotides contains a D-loop stem structure and the at least four contiguous guanosine-containing nucleotides are located at the 5' end of the neuroprotective molecule. Also provided are methods of inducing or increasing stress granule formation in a cell, decreasing protein translation in a cell, decrease stress-induced cell death, or treating a neurological disorder associated with neuron death in a subject using at least one of these neuroprotective molecules or a C-myc oligonucleotide. Also provided are methods of identifying a candidate translation inhibitory nucleic acid.La présente invention concerne des molécules neuroprotectrices contenant une séquence de 25-35 nucléotides contigus qui est au moins identique à 80 % à une séquence contiguë entre le nucléotide 1 et le nucléotide 50 d'un ARNt humain mature et au moins quatre nucléotides contigus contenant de la guanosine, dans lesquelles la séquence de 25
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