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.