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KMID : 1140120110160030210
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Cancer Prevention Research
2011 Volume.16 No. 3 p.210 ~ p.215
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Peptide Therapeutics for the Prevention of Cancers and Cardiovascular Diseases: The Special Value of the PGC-1α Pathway
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di Luccio Eric
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Abstract
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The transcriptional coactivator peroxisome proliferator-activated receptor coactivator-1α (PGC-1α/Ppargc1α) plays a central role in controlling and modulating the expression of mitochondrial genes. High levels of PGC-1α are linked to numerous pathological conditions and multiple pathways in relation with ROS detoxification, cancers, Alzheimer’s disease, stress response, circadian clock function, hepatic metabolism, strokes, cardiovascular diseases, Huntington’s disease and aging. PGC-1α has been cited as a potential new therapeutic target in the prevention of cancers and cardiovascular diseases by the mean of modulating the PGC-1α dependent-pathways using peptides targeting the Leu-Xaa-Xaa- Leu-Leu (LxxLL) domain of PGC-1α. LxxLL functional domain is key in many protein-protein interactions. New therapeutics are sorely needed to prevent and cure cancers along with the deterrence of cardiovascular diseases. In this study, using computational modeling tools, we provide structural insights into the design of small peptides to mimic the PGC-1α LxxLL domain to compete against PGC-1α in a bid to ultimately regulate the pathway.
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KEYWORD
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Transcription co-regulators, Epigenetic therapy of cancer, PGC-1α, Cardiovascular diseases
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