Heme Stabilization of α-Synuclein Oligomers during Amyloid Fibril Formation

Eric Y. Hayden, Prerna Kaur, Thomas L. Williams, Hiroshi Matsui, Syun-Ru Yeh, Denis L. Rousseau

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

α-Synuclein (αSyn), which forms amyloid fibrils, is linked to the neuronal pathology of Parkinson's disease, as it is the major fibrillar component of Lewy bodies, the inclusions that are characteristic of the disease. Oligomeric structures, common to many neurodegenerative disease-related proteins, may in fact be the primary toxic species, while the amyloid fibrils exist either as a less toxic dead-end species or even as a beneficial mechanism for clearing damaged proteins. To alter the progression of the aggregation and gain insights into the prefibrillar structures, we determined the effect of heme on αSyn oligomerization by several different techniques, including native (nondenaturing) polyacrylamide gel electrophoresis, thioflavin T fluorescence, transmission electron microscopy, atomic force microscopy, circular dichroism, and membrane permeation using a calcein release assay. During aggregation, heme is able to bind the αSyn in a specific fashion, stabilizing distinct oligomeric conformations and promoting the formation of αSyn into annular structures, thereby delaying and/or inhibiting the fibrillation process. These results indicate that heme may play a regulatory role in the progression of Parkinson's disease; in addition, they provide insights into how the aggregation process may be altered, which may be applicable to the understanding of many neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)4599-4610
Number of pages12
JournalBiochemistry
Volume54
Issue number30
DOIs
StatePublished - Aug 4 2015

Fingerprint

Synucleins
Heme
Oligomers
Amyloid
Stabilization
Neurodegenerative diseases
Agglomeration
Poisons
Neurodegenerative Diseases
Parkinson Disease
Native Polyacrylamide Gel Electrophoresis
Lewy Bodies
Oligomerization
Atomic Force Microscopy
Cytomegalovirus Infections
Pathology
Circular Dichroism
Electrophoresis
Transmission Electron Microscopy
Permeation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Heme Stabilization of α-Synuclein Oligomers during Amyloid Fibril Formation. / Hayden, Eric Y.; Kaur, Prerna; Williams, Thomas L.; Matsui, Hiroshi; Yeh, Syun-Ru; Rousseau, Denis L.

In: Biochemistry, Vol. 54, No. 30, 04.08.2015, p. 4599-4610.

Research output: Contribution to journalArticle

Hayden, Eric Y. ; Kaur, Prerna ; Williams, Thomas L. ; Matsui, Hiroshi ; Yeh, Syun-Ru ; Rousseau, Denis L. / Heme Stabilization of α-Synuclein Oligomers during Amyloid Fibril Formation. In: Biochemistry. 2015 ; Vol. 54, No. 30. pp. 4599-4610.
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