title: Novel Nuclear Factor-KappaB Targeting Peptide Suppresses β-Amyloid Induced Inflammatory and Apoptotic Responses in Neuronal Cells.
abstract: In the central nervous system (CNS), activation of the transcription factor nuclear factor-kappa B (NF-κβ) is associated with both neuronal survival and increased vulnerability to apoptosis. The mechanisms underlying these dichotomous effects are attributed to the composition of NF-κΒ dimers. In Alzheimer's disease (AD), β-amyloid (Aβ) and other aggregates upregulate activation of p65:p50 dimers in CNS cells and enhance transactivation of pathological mediators that cause neuroinflammation and neurodegeneration. Hence selective targeting of activated p65 is an attractive therapeutic strategy for AD. Here we report the design, structural and functional characterization of peptide analogs of a p65 interacting protein, the glucocorticoid induced leucine zipper (GILZ). By virtue of binding the transactivation domain of p65 exposed after release from the inhibitory IκΒ proteins in activated cells, the GILZ analogs can act as highly selective inhibitors of activated p65 with minimal potential for off-target effects.
authors.affiliation: School of Dentistry, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Mythily
authors.initials: M
authors.lastname: Srinivasan
authors.affiliation: Institute of Psychiatry Research, Department of Psychiatry and Medical & Molecular Genetics, School of Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Baindu
authors.initials: B
authors.lastname: Bayon
authors.affiliation: Institute of Psychiatry Research, Department of Psychiatry and Medical & Molecular Genetics, School of Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Nipun
authors.initials: N
authors.lastname: Chopra
authors.affiliation: Institute of Psychiatry Research, Department of Psychiatry and Medical & Molecular Genetics, School of Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Debomoy K
authors.initials: DK
authors.lastname: Lahiri
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005333:Fetus / Q000166:cytology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053583:Interleukin-1beta; D015850:Interleukin-6; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; C404226:TSC22D3 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D053148:Caspase 3; D053453:Caspase 9