title: Rescuing neuronal cell death by RAIDD- and PIDD- derived peptides and its implications for therapeutic intervention in neurodegenerative diseases.
abstract: Caspase-2 is known to be involved in oxidative-stress mediated neuronal cell death. In this study, we demonstrated that rotenone-induced neuronal cell death is mediated by caspase-2 activation via PIDDosome formation. Our newly designed TAT-fused peptides, which contains wild-type helix number3 (H3) from RAIDD and PIDD, blocked the PIDDosome formation in vitro. Furthermore, peptides inhibited rotenone-induced caspase-2-dependent apoptosis in neuronal cells. These results suggest that PIDD- or RAIDD-targeted peptides might be effective at protecting against rotenone-induced neurotoxicity. Our peptides are novel neuronal cell apoptosis inhibitors that might serve as a prototype for development of drugs for the treatment of neurodegenerative diseases.
authors: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 38541, South Korea.
authors: Tae-Ho
authors: TH
authors: Jang
authors: Department of Anatomy, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong Nam-Gu, Daegu 42415, South Korea.
authors: In-Hye
authors: IH
authors: Lim
authors: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 38541, South Korea.
authors: Chang Min
authors: CM
authors: Kim
authors: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 38541, South Korea.
authors: Jae Young
authors: JY
authors: Choi
authors: Department of Anatomy, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong Nam-Gu, Daegu 42415, South Korea.
authors: Eun-Ae
authors: EA
authors: Kim
authors: Department of Anatomy, College of Medicine, Yeungnam University, 317-1 Daemyung-Dong Nam-Gu, Daegu 42415, South Korea.
authors: Tae-Jin
authors: TJ
authors: Lee
authors: School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan 38541, South Korea.
authors: Hyun Ho
authors: HH
authors: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053420:CRADD Signaling Adaptor Protein / Q000737:chemistry*; D053143:Caspase 2 / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000737:chemistry*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
chemical_list: D053420:CRADD Signaling Adaptor Protein; C104252:CRADD protein, human; D057846:Cell-Penetrating Peptides; D053418:Death Domain Receptor Signaling Adaptor Proteins; C485896:PIDD1 protein, human; C490360:CASP2 protein, human; C490359:Casp2 protein, rat; D053143:Caspase 2; D003546:Cysteine Endopeptidases