Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments

Omar M.A. El-Agnaf; Ross Jakes; Martin D. Curran; Derek Middleton; Raffaele Ingenito; Elisabetta Bianchi; Antonello Pessi; David Neill; Andrew Wallace

doi:10.1016/S0014-5793(98)01418-5

Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments

Omar M.A. El-Agnaf, Ross Jakes, Martin D. Curran, Derek Middleton, Raffaele Ingenito, Elisabetta Bianchi, Antonello Pessi, David Neill, Andrew Wallace

Research output: Contribution to journal › Article › peer-review

336 Citations (Scopus)

Abstract

α-Synuclein (α-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 α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild-type α-syn, mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. Here we report that aggregates of NAC and α-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of α-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases. Copyright (C) 1998 Federation of European Biochemical Societies.

Original language	English
Pages (from-to)	71-75
Number of pages	5
Journal	FEBS Letters
Volume	440
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-5793(98)01418-5
Publication status	Published - Nov 27 1998
Externally published	Yes

Keywords

Amyloid
Lewy body
Neurodegenerative disease
Parkinson's disease
Toxicity
α-Synuclein

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/S0014-5793(98)01418-5

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El-Agnaf, O. M. A., Jakes, R., Curran, M. D., Middleton, D., Ingenito, R., Bianchi, E., Pessi, A., Neill, D., & Wallace, A. (1998). Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments. FEBS Letters, 440(1-2), 71-75. https://doi.org/10.1016/S0014-5793(98)01418-5

Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments. / El-Agnaf, Omar M.A.; Jakes, Ross; Curran, Martin D. et al.
In: FEBS Letters, Vol. 440, No. 1-2, 27.11.1998, p. 71-75.

Research output: Contribution to journal › Article › peer-review

El-Agnaf, OMA, Jakes, R, Curran, MD, Middleton, D, Ingenito, R, Bianchi, E, Pessi, A, Neill, D & Wallace, A 1998, 'Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments', FEBS Letters, vol. 440, no. 1-2, pp. 71-75. https://doi.org/10.1016/S0014-5793(98)01418-5

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title = "Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments",

abstract = "α-Synuclein (α-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 α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild-type α-syn, mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. Here we report that aggregates of NAC and α-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of α-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases. Copyright (C) 1998 Federation of European Biochemical Societies.",

keywords = "Amyloid, Lewy body, Neurodegenerative disease, Parkinson's disease, Toxicity, α-Synuclein",

author = "El-Agnaf, {Omar M.A.} and Ross Jakes and Curran, {Martin D.} and Derek Middleton and Raffaele Ingenito and Elisabetta Bianchi and Antonello Pessi and David Neill and Andrew Wallace",

note = "Funding Information: We would like to thank Mr R. Murphy, School of Chemistry, QUB for assistance with the CD work and Ms O. O'Shea and Mr P. Larkin, School of Biomedical Science, QUB for their assistance with the EM work. We would also like to thank Mrs A. Healy of the School of Biology and Biochemistry, QUB for assistance with the cytotoxicity staining. This work was supported by funding from the UK Medical Research Council (Grant G9626372N). ",

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AU - Jakes, Ross

AU - Curran, Martin D.

AU - Middleton, Derek

AU - Ingenito, Raffaele

AU - Bianchi, Elisabetta

AU - Pessi, Antonello

AU - Neill, David

AU - Wallace, Andrew

N1 - Funding Information: We would like to thank Mr R. Murphy, School of Chemistry, QUB for assistance with the CD work and Ms O. O'Shea and Mr P. Larkin, School of Biomedical Science, QUB for their assistance with the EM work. We would also like to thank Mrs A. Healy of the School of Biology and Biochemistry, QUB for assistance with the cytotoxicity staining. This work was supported by funding from the UK Medical Research Council (Grant G9626372N).

PY - 1998/11/27

Y1 - 1998/11/27

N2 - α-Synuclein (α-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 α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild-type α-syn, mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. Here we report that aggregates of NAC and α-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of α-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases. Copyright (C) 1998 Federation of European Biochemical Societies.

AB - α-Synuclein (α-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 α-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We have shown that human wild-type α-syn, mutant α-syn(Ala30Pro) and mutant α-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. Here we report that aggregates of NAC and α-syn proteins induced apoptotic cell death in human neuroblastoma SH-SY5Y cells. These findings indicate that accumulation of α-syn and its degradation products may play a major role in the development of the pathogenesis of these neurodegenerative diseases. Copyright (C) 1998 Federation of European Biochemical Societies.

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Aggregates from mutant and wild-type α-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β-sheet and amyloid-like filaments

Abstract

Keywords

ASJC Scopus subject areas

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