title: Aggregates from mutant and wild-type alpha-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of beta-sheet and amyloid-like filaments.
abstract: Alpha-synuclein (alpha-syn) protein and a fragment of it, called NAC, have been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild-type alpha-syn, mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. Here we report that aggregates of NAC and alpha-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of alpha-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases.
authors.affiliation: Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Queen's University Belfast, UK. o.elagnaf@qub.ac.uk
authors.forename: O M
authors.initials: OM
authors.lastname: El-Agnaf
authors.forename: R
authors.initials: R
authors.lastname: Jakes
authors.forename: M D
authors.initials: MD
authors.lastname: Curran
authors.forename: D
authors.initials: D
authors.lastname: Middleton
authors.forename: R
authors.initials: R
authors.lastname: Ingenito
authors.forename: E
authors.initials: E
authors.lastname: Bianchi
authors.forename: A
authors.initials: A
authors.lastname: Pessi
authors.forename: D
authors.initials: D
authors.lastname: Neill
authors.forename: A
authors.initials: A
authors.lastname: Wallace
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis; D052160:Benzothiazoles; D001704:Biopolymers / Q000378:metabolism / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002942:Circular Dichroism; D006801:Humans; D008854:Microscopy, Electron; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009447:Neuroblastoma; D019636:Neurodegenerative Diseases / Q000209:etiology; D009474:Neurons / Q000166:cytology*; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics; D010455:Peptides / Q000378:metabolism / Q000502:physiology; D017433:Protein Structure, Secondary; D051843:Synucleins; D013844:Thiazoles; D014407:Tumor Cells, Cultured; D051844:alpha-Synuclein
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D001704:Biopolymers; D009419:Nerve Tissue Proteins; D010455:Peptides; C497604:SNCA protein, human; D051843:Synucleins; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T