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Investigating the Binding Affinity of the Peptide Humanin and its Analogs to Amyloid Beta
Author(s) -
Esckilsen Daniel Edward,
Guttikonda Prathyusha,
Iwaniec Brandon William Joseph,
Evans Hedeel,
Milletti Maria C,
HeylClegg Deborah
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.601.10
Subject(s) - neuroprotection , peptide , amyloid (mycology) , p3 peptide , amyloid precursor protein , peptide sequence , amyloid beta , bace1 as , receptor , biochemistry , chemistry , alzheimer's disease , biology , microbiology and biotechnology , neuroscience , medicine , disease , gene , inorganic chemistry
Mitochondrial dysfunction has been proposed as a trigger and an early event in the pathology of Alzheimer's disease. Humanin is a 24‐residue, mitochondrially‐encoded peptide, known to exhibit strong neuro‐ and cyto‐protective effects in Alzheimer's disease models. Amino acid residues 5–15 of humanin have been previously shown to interact with residues 17–28 of amyloid‐β, the main component of amyloid plaques, found as extracellular deposits in the brains of Alzheimer's patients. As both Amyloid β and humanin are known to activate the same G protein‐coupled receptor, FPRL1, it is likely that humanin exhibits its cytoprotective effects by regulating access of Amyloid β to the receptor ultimately modulating the Erk1/2 signaling cascade. In addition to mitochondrially‐encoded humanin, ten different nuclear‐encoded analogs have been identified with little or no known function. Using cloning, molecular dynamics, peptide synthesis, Western blotting, immunoprecipitation, and tissue culture, we investigate the contribution of certain amino acid residues of humanin to its binding affinity to Amyloid β and their neuroprotective effects on amyloid β‐induced toxicity in PC12 cells. Support or Funding Information Provost Research Support Award, The Chemistry Department Sellers Fund, Eastern Michigan University