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1. (WO2018132755) COMPOSITIONS AND METHODS FOR DISRUPTING THE MOLECULAR MECHANISMS ASSOCIATED WITH MITOCHONDRIAL DYSFUNCTION AND NEURODEGENERATIVE DISEASE

Pub. No.:    WO/2018/132755    International Application No.:    PCT/US2018/013645
Publication Date: Fri Jul 20 01:59:59 CEST 2018 International Filing Date: Sat Jan 13 00:59:59 CET 2018
IPC: C12Q 1/68
C40B 30/04
C40B 40/08
C12N 15/113
C12N 15/63
A61K 9/127
A61K 31/7088
Applicants: DUKE UNIVERSITY
Inventors: LARSEN, Peter Anthony
Title: COMPOSITIONS AND METHODS FOR DISRUPTING THE MOLECULAR MECHANISMS ASSOCIATED WITH MITOCHONDRIAL DYSFUNCTION AND NEURODEGENERATIVE DISEASE
Abstract:
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.