alpha-Synuclein is a 14 kDa protein encoded by the SNCA gene that is abundantly expressed in neurons. Within the neuron, alpha-Synuclein is densely localized on presynaptic terminals, indicating a potential role in synaptic transmission. Nitration at specific tyrosine residues promotes misfolding and aggregation of alpha-Synuclein. These aggregates are a major component of Lewy bodies, characteristic lesions of neurodegenerative disorders known as synucleinopathies. Synucleinopathies include Parkinson’s disease, Alzheimer’s disease, dementia with Lewy bodies, and others. Mutations in the SNCA gene have been linked to autosomal dominant hereditary Parkinson’s disease (1). Recent studies suggest that alpha-Synuclein may interfere with neuroprotective pathways such as insulin signaling (2).It is still unclear exactly how alpha-Synuclein aggregates contribute to the neuronal damage associated with these conditions.
Giasson et. al. characterized the alpha-Synuclein (Nitrate Tyr125, Nitrate Tyr133) antibody which opened the doors to studying the physiologic consequences of alpha-Synuclein nitration (3). The alpha-Synuclein antibody allowed the group to localize nitrated alpha-Synuclein to the sites of neuronal oxidative damage, suggesting a potential role in the pathogenesis of neurodegeneration. Shavali et. al. used the alpha-Synuclein antibody to determine the localization of alpha-Synuclein protein within overexpressing cells (4). The group found that overexpressed alpha-Synuclein localizes to the mitochondria and hypersensitizes the cell to mitochondrial toxins, suggesting a mechanism for its cytotoxicity.
Meanwhile, Herva et. al. sought to develop a high throughput system for screening anti-amyloid compounds against alpha-Synuclein aggregates (5). The group used the alpha-Synuclein antibody to develop a method similar to the protein misfolding cyclic amplification (PMCA) technique used for making prion aggregates. They used the alpha-Synuclein antibody to screen compounds against their alpha-Synuclein PMCA aggregates, using western blot to determine aggregate size and thus drug efficacy. All together, the group developed a rapid and reproducible method for screening novel therapeutics for these common neurodegenerative disorders.
Novus Biologicals offers alpha-Synuclein reagents for your research needs including:
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