Detecting morphologically distinct oligomeric forms of α-synuclein

Sharareh Emadi, Srinath Kasturirangan, Min S. Wang, Philip Schulz, Michael Sierks

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Neuropathologic and genetics studies as well as transgenic animal models have provided strong evidence linking misfolding and aggregation of α-synuclein to the progression of Parkinson disease (PD) and other related disorders. A growing body of evidence implicates various oligomeric forms of α-synuclein as the toxic species responsible for neurodegeneration and neuronal cell death. Although numerous different oligomeric forms of α-synuclein have been identified in vitro, it is not known which forms are involved in PD or how, when, and where different forms contribute to the progression of PD. Reagents that can interact with specific aggregate forms of α-synuclein would be very useful not only as tools to study how different aggregate forms affect cell function, but also as potential diagnostic and therapeutic agents for PD. Here we show that a single chain antibody fragment (syn-10H scFv) isolated from a phage display antibody library binds to a larger, later stage oligomeric form of α-synuclein than a previously reported oligomeric specific scFv isolated in our laboratory. The scFv described here inhibits aggregation of α-synuclein in vitro, blocks extracellular α-synuclein-induced toxicity in both undifferentiated and differentiated human neuroblastoma cell lines (SH-SY5Y), and specifically recognizes naturally occurring aggregates in PD but not in healthy human brain tissue.

Original languageEnglish (US)
Pages (from-to)11048-11058
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number17
DOIs
StatePublished - Apr 24 2009

Fingerprint

Synucleins
Parkinson Disease
Agglomeration
Single-Chain Antibodies
Immunoglobulin Fragments
Genetically Modified Animals
Bacteriophages
Poisons
Cell death
Neuroblastoma
Toxicity
Brain
Animals
Cell Death
Animal Models
Display devices
Cells
Tissue
Cell Line
Antibodies

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Detecting morphologically distinct oligomeric forms of α-synuclein. / Emadi, Sharareh; Kasturirangan, Srinath; Wang, Min S.; Schulz, Philip; Sierks, Michael.

In: Journal of Biological Chemistry, Vol. 284, No. 17, 24.04.2009, p. 11048-11058.

Research output: Contribution to journalArticle

Emadi, Sharareh ; Kasturirangan, Srinath ; Wang, Min S. ; Schulz, Philip ; Sierks, Michael. / Detecting morphologically distinct oligomeric forms of α-synuclein. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 17. pp. 11048-11058.
@article{86c2892be79643b1ac0cf7a64a885323,
title = "Detecting morphologically distinct oligomeric forms of α-synuclein",
abstract = "Neuropathologic and genetics studies as well as transgenic animal models have provided strong evidence linking misfolding and aggregation of α-synuclein to the progression of Parkinson disease (PD) and other related disorders. A growing body of evidence implicates various oligomeric forms of α-synuclein as the toxic species responsible for neurodegeneration and neuronal cell death. Although numerous different oligomeric forms of α-synuclein have been identified in vitro, it is not known which forms are involved in PD or how, when, and where different forms contribute to the progression of PD. Reagents that can interact with specific aggregate forms of α-synuclein would be very useful not only as tools to study how different aggregate forms affect cell function, but also as potential diagnostic and therapeutic agents for PD. Here we show that a single chain antibody fragment (syn-10H scFv) isolated from a phage display antibody library binds to a larger, later stage oligomeric form of α-synuclein than a previously reported oligomeric specific scFv isolated in our laboratory. The scFv described here inhibits aggregation of α-synuclein in vitro, blocks extracellular α-synuclein-induced toxicity in both undifferentiated and differentiated human neuroblastoma cell lines (SH-SY5Y), and specifically recognizes naturally occurring aggregates in PD but not in healthy human brain tissue.",
author = "Sharareh Emadi and Srinath Kasturirangan and Wang, {Min S.} and Philip Schulz and Michael Sierks",
year = "2009",
month = "4",
day = "24",
doi = "10.1074/jbc.M806559200",
language = "English (US)",
volume = "284",
pages = "11048--11058",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "17",

}

TY - JOUR

T1 - Detecting morphologically distinct oligomeric forms of α-synuclein

AU - Emadi, Sharareh

AU - Kasturirangan, Srinath

AU - Wang, Min S.

AU - Schulz, Philip

AU - Sierks, Michael

PY - 2009/4/24

Y1 - 2009/4/24

N2 - Neuropathologic and genetics studies as well as transgenic animal models have provided strong evidence linking misfolding and aggregation of α-synuclein to the progression of Parkinson disease (PD) and other related disorders. A growing body of evidence implicates various oligomeric forms of α-synuclein as the toxic species responsible for neurodegeneration and neuronal cell death. Although numerous different oligomeric forms of α-synuclein have been identified in vitro, it is not known which forms are involved in PD or how, when, and where different forms contribute to the progression of PD. Reagents that can interact with specific aggregate forms of α-synuclein would be very useful not only as tools to study how different aggregate forms affect cell function, but also as potential diagnostic and therapeutic agents for PD. Here we show that a single chain antibody fragment (syn-10H scFv) isolated from a phage display antibody library binds to a larger, later stage oligomeric form of α-synuclein than a previously reported oligomeric specific scFv isolated in our laboratory. The scFv described here inhibits aggregation of α-synuclein in vitro, blocks extracellular α-synuclein-induced toxicity in both undifferentiated and differentiated human neuroblastoma cell lines (SH-SY5Y), and specifically recognizes naturally occurring aggregates in PD but not in healthy human brain tissue.

AB - Neuropathologic and genetics studies as well as transgenic animal models have provided strong evidence linking misfolding and aggregation of α-synuclein to the progression of Parkinson disease (PD) and other related disorders. A growing body of evidence implicates various oligomeric forms of α-synuclein as the toxic species responsible for neurodegeneration and neuronal cell death. Although numerous different oligomeric forms of α-synuclein have been identified in vitro, it is not known which forms are involved in PD or how, when, and where different forms contribute to the progression of PD. Reagents that can interact with specific aggregate forms of α-synuclein would be very useful not only as tools to study how different aggregate forms affect cell function, but also as potential diagnostic and therapeutic agents for PD. Here we show that a single chain antibody fragment (syn-10H scFv) isolated from a phage display antibody library binds to a larger, later stage oligomeric form of α-synuclein than a previously reported oligomeric specific scFv isolated in our laboratory. The scFv described here inhibits aggregation of α-synuclein in vitro, blocks extracellular α-synuclein-induced toxicity in both undifferentiated and differentiated human neuroblastoma cell lines (SH-SY5Y), and specifically recognizes naturally occurring aggregates in PD but not in healthy human brain tissue.

UR - http://www.scopus.com/inward/record.url?scp=66449097646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66449097646&partnerID=8YFLogxK

U2 - 10.1074/jbc.M806559200

DO - 10.1074/jbc.M806559200

M3 - Article

C2 - 19141614

AN - SCOPUS:66449097646

VL - 284

SP - 11048

EP - 11058

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 17

ER -