Alpha-synuclein (alpha-Syn), a small (14 kDa) protein associated with Parkinson's disease, is abundant in human neural tissues. alpha-Syn plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals; however, the mechanism by which it performs this function are not well understood. In addition, there is a correlation between alpha-Syn over-expression and upregulation of an innate immune response. Given the growing body of literature surrounding antimicrobial peptides (AMPs) in the brain, and the similarities between alpha-Syn and a previously characterized AMP, Amyloid-beta, we set out to investigate if alpha-Syn shares AMP-like properties. Here we demonstrate that alpha-Syn exhibits antibacterial activity against Escherichia coli and Staphylococcus aureus. In addition, we demonstrate a role for cc-Syn in inhibiting various pathogenic fungal strains such as Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani. We also analyzed localizations of recombinant alpha-Syn protein in E. coli and Candida albicans. These results suggest that in addition to alpha-Syn's role in neurotransmitter release, it appears to be a natural AMP. (C) 2016 Elsevier Inc. All rights reserved.