公开(公告)号：WO2018132755A1

公开(公告)日：2018-07-19

申请号：PCT/US2018/013645

申请日：2018-01-12

申请人： DUKE UNIVERSITY

发明人： LARSEN, Peter Anthony

IPC分类号： C12Q1/68 ,  C40B30/04 ,  C40B40/08 ,  C12N15/113 ,  C12N15/63 ,  A61K9/127 ,  A61K31/7088

CPC分类号： C12N15/113 ,  A61K31/7088 ,  C12N2310/11 ,  C12N2310/20 ,  C12Q1/6883 ,  C12Q2600/154 ,  C12Q2600/156 ,  C12Q2600/178

摘要： Retrotransposons, operating though human-specific neurological pathways, can contribute to environment, lifestyle, and/or age-related neurodegeneration by disrupting functional mitochondrial populations within neurons. The mitochondrial disruption can occur through a number of retrotransposon-induced mechanisms that can influence the efficient and accurate transcription and/or translation of mitochondrial genes encoded in the nuclear genome, operating primarily through epigenetic processes. Alu element-related conformational changes (both subtle and major) of the outer and inner mitochondrial membrane pores can restrict or prevent the normal translocation of proteins (i.e., TOMM and TIMM complexes), ultimately contributing to mitochondrial stress, mitophagy, inflammation, and neuron and glial cell death. Compositions and methods are provided for mitigating and/or preventing Alu element-induced conformational changes to prevent and/or treat neurodegenerative disease and other diseases and disorders associated with at least one TOMM, TIMM, or APOE isoform including cancer and other inflammatory diseases.