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Journal article
Heptamer Peptide Disassembles Native Amyloid in Human Plasma Through Heat Shock Protein 70
Rejuvenation research, v 21(6), pp 527-534
01 Dec 2018
PMID: 29651925
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Proteostasis, which includes the repair and disposal of misfolded proteins, depends, in part, on the activity of heat shock proteins (HSPs), a well-known class of chaperone molecules. When this process fails, abnormally folded proteins may accumulate in cells, tissues, and blood. These species are a hallmark of protein aggregation diseases, but also amass during aging, often in the absence of an identified clinical disorder. We report that a neuroprotective cyclic heptapeptide, CHEC-7, which has been applied systemically as a therapeutic in animal neurodegeneration models, disrupts such aggregates and inhibits amyloidogenesis when added in nanomolar concentrations to human plasma. This effect includes aggregates of amyloid beta (A1-40, 1-42), prominent features of Alzheimer's disease pathology. The activity of endogenous HSP70, a recently discovered target of the peptide, is required as demonstrated by both antibody blocking and application of pifithrin-, an HSP70 inhibitor. CHEC-7 is the first high-affinity compound to stimulate HSP70's disaggregase activity and therefore enable this endogenous mechanism in a human systemic environment, increasing the likelihood of a convenient therapy for protein aggregate disease, including age-related failures of protein repair.
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Details
- Title
- Heptamer Peptide Disassembles Native Amyloid in Human Plasma Through Heat Shock Protein 70
- Creators
- Timothy J. Cunningham - Drexel UniversityJeffrey Greenstein - Multiple Sclerosis Research InstituteLihua Yao - Drexel UniversityItzhak Fischer - Drexel UniversityTheresa Connors - Drexel University
- Publication Details
- Rejuvenation research, v 21(6), pp 527-534
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 8
- Grant note
- Pennsylvania Department of Health NS055976 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Commonwealth Universal Research Enhancement Program
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000434489900001
- Scopus ID
- 2-s2.0-85058902021
- Other Identifier
- 991019169067104721
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- Web of Science research areas
- Geriatrics & Gerontology