Newmarket Scientific: First Commercially Available Active Human and Mouse ASYN Proteins from StressMarq

Alpha-synuclein is a 140 amino acid protein which in humans, is encoded by the SNCA gene. It is expressed predominantly in the brain and particularly in presynaptic nerve terminals.

Due to its structural flexibility, alpha-synuclein can adopt several conformations and depending on the environment and the binding partners, exists as a dynamic balance between monomeric unfolded and an amphipathic alpha-helix (membrane binding) states.

In healthy brains, quality control systems ensure the correct assembly of alpha-synucleins and intracellular alpha-synuclein homeostasis is controlled via the ubiquitin-proteasome system and the lysosomal autophagy system, with the latter being involved in clearing oligomer assemblies. Other synucleins are also able to inhibit and control the oligomerisation of alpha-synuclein.

Failure in these systems, oxidative stress, pH changes are, to name a few, examples of triggers that can lead to the overproduction and accumulation of alpha-synuclein. In addition, post-translational modifications of alpha-synuclein can lead to a change in conformation resulting in the alpha-synuclein proteins being more susceptible to aggregation. In Lewy bodies, it has been shown that phosphorylated Ser129 alpha-synuclein is the most abundant form of alpha-synuclein present in these aggregates.

In pathological conditions such as Parkinson’s disease, soluble alpha-synuclein monomers associate to form oligomers that will combine further to generate protofibrils that subsequently aggregate to form large and insoluble aggregates, the main component of Lewy body inclusions.[1] These neurotoxic aggregates will cause the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, causing the motor symptoms in PD. [2]

StressMarq has recently released the first commercially available active Human and Mouse Alpha Synuclein Monomers and Pre-formed Fibrils:

- Active Human Recombinant Alpha Synuclein Protein Monomer (Cat No. SPR-321)
- Active Human Recombinant Alpha Synuclein Pre-Formed Fibrils (Cat No. SPR-322).
- Active Mouse Recombinant Alpha Synuclein Protein Monomer (Cat No. SPR-323)
- Active Human Recombinant Alpha Synuclein Pre-Formed Fibrils (Cat No. SPR-324).

The active alpha synuclein pre-formed fibrils (Cat No. SPR-322) in presence of the active alpha-syn monomer (SPR-321) has been shown to induce Lewy body inclusion formation in neuronal cell culture, a characteristic of Parkinson’s Disease.

This was demonstrated using T-thioflavin, a fluorescent dye that binds to beta sheet-rich structures, such as those in α-Syn aggregates and which upon binding, experiences a red-shift in its emission spectrum and increased fluorescence intensity. As seen in the images below, it was shown that 10 nM of active α-Syn aggregate (SPR-322) combined with 100 µm of active α-Syn monomer (SPR-321) could induce aggregation, as compared to active α-Syn aggregate (SPR-322) and active α-Syn monomer (SPR-321) alone.

A similar experiment was also performed to show the activity of the active mouse pre-formed fibrils and monomers (SPR 323 and SPR324).

In addition, StressMarq has also launched control alpha synuclein protein monomers (Cat No. SPR-316) and control alpha synuclein protein aggregates (Cat No. SPR-317) which are inactive as shown in the image below.

These active alpha synuclein proteins and the related alpha synuclein antibodies below can be purchased in the UK and Ireland via Newmarket Scientific, the distributor of StressMarq.

StressMarq alpha synuclein antibodies:	Cat. No.
Alpha synuclein, clone 3C11	SMC-530
Alpha synuclein, clone 10H7	SMC-531
Alpha synuclein, clone 3F8	SMC-532
Alpha synuclein, clone 4F1	SMC-533
Alpha synuclein pSer129	SPC-742