Alpha Synuclein Constructs for Neurodegenerative Disease Research

StressMarq has developed unique alpha synuclein constructs to provide invaluable support to researchers engaged in disease model development and the advancement of neurodegenerative disease research and drug discovery.

The company offers a diverse array of innovative monomeric, oligomeric, and fibrillar alpha synuclein constructs, tailored specifically for neurodegenerative disease research.

Alpha Synuclein Constructs for Neurodegenerative Disease Research

Alpha synuclein is a key protein for neurodegenerative disease research and drug discovery. A small protein widely present in the brain, particularly in the presynaptic terminals of neurons, alpha synuclein (α-syn) is characterized by its high solubility and lack of intrinsic structure. This protein plays a pivotal role in neuronal signaling, specifically in the release of synaptic vesicles that transmit important neurotransmitters like dopamine, crucial for proper movement control.

Alpha synuclein has a propensity to form aggregates of various types, including oligomeric and fibrillary structures. The soluble, misfolded aggregates of alpha synuclein have been identified as neurotoxic agents and can spread diseases in a prion-like manner. These “synucleinopathies” encompass several neurodegenerative disorders, including Parkinson’s disease, dementia with Lewy bodies, and Multiple System Atrophy. The pathogenesis of these conditions is closely linked to the misfolding of alpha synuclein. The aggregation of alpha synuclein is considered a hallmark of Parkinson’s disease, and different forms of the protein can be utilized to develop accurate disease models.

To help researchers utilize alpha synuclein in their neurodegenerative disease research and drug discovery applications, StressMarq has developed a groundbreaking range of monomeric, oligomeric, and fibrillar alpha synuclein constructs.

Alpha Synuclein Pre-formed Fibrils (PFFs), Oligomers, & Monomers

The development of robust disease models plays a pivotal role in uncovering the underlying pathological mechanisms, evaluating the effectiveness of therapeutic interventions, and assessing the safety profiles of potential drug candidates.

Alpha Synuclein Pre-formed Fibrils (PFFs)

In comparison to conventional disease modeling methods, the utilization of Alpha Synuclein Pre-formed Fibrils (PFFs) offers distinct advantages as it does not rely on gene editing, chemical manipulation, or physical damage to induce pathology. Instead, PFFs have the unique ability to closely mimic the naturally occurring pathological states and processes associated with neurodegenerative diseases. Alpha Synuclein Pre-formed Fibrils (PFFs) are utilized to seed the aggregation of endogenous alpha synuclein in cultured cells or animal brains, enabling the construction of models that recapitulate key aspects of the disease. PFFs provide novel means and a highly advantageous approach to modeling neurodegenerative diseases.

StressMarq’s pre-formed fibrils (PFFs) of alpha synuclein serve as powerful catalysts, triggering the formation of fresh fibrils from active alpha-synuclein monomers. These PFFs have proven to be exceptionally valuable tools in inducing endogenous alpha synuclein phosphorylation and facilitating the formation of Lewy body inclusions within neuronal cell cultures. Moreover, they find extensive utility in in vitro oligomerization studies, enabling researchers to investigate the intricate processes underlying the aggregation of alpha synuclein.

StressMarq’s Alpha Synuclein PFFs (red) cat#SPR-322, were shown to be taken up by SH-SY5Y cells and transmitted to neuronal iPSCs within 14 days. Blue: Hoechst/DNA; Green: SHSY5Y-GFP; Red: alpha synuclein PFFs-555 (cat#SPR-322); Purple: Tubulin.
Immunocytochemistry/Immunofluorescence analysis of human iPSC-derived neurons treated with alpha synuclein pre-formed fibrils (SPR-322). Primary Antibody: Mouse Anti-Alpha Synuclein (pSer129) Monoclonal Antibody (SMC-600) at 1:1000 for O/N at 4°C. Secondary Antibody: Anti-Rabbit: A488 at 1:1000 for 1 hour at RT. Magnification: 40X. Nuclear stain: Hoechst- 20 min, RT (blue). Actin stain: Phalloidin-647- 20 min, RT (magenta). 4K cells per well. iPSC neurons: Applied StemCell Catalog # ASE-9321K. A) negative control; no fibrils added to well. B) 7 days after the addition of active recombinant human pre-formed fibrils (Type 1). Fibrils were sonicated before use and applied 2.5 ug per well

Alpha Synuclein Oligomers 

In synucleinopathies, there is a growing recognition that alpha-synuclein oligomers represent the highly toxic species. StressMarq has developed kinetically stable alpha synuclein oligomers that have been shown to exhibit toxicity toward dopaminergic neurons. These oligomers also induce phosphorylation of alpha-synuclein at Ser129, a hallmark associated with Parkinson’s disease. Notably, these toxic alpha-synuclein oligomers are generated without the need for any additional inducers or inhibitors, enhancing their relevance for disease modeling.

In addition, StressMarq offers dopamine-stabilized alpha synuclein oligomers and EGCG-stabilized alpha synuclein oligomers. By leveraging dopamine or EGCG, researchers can stabilize alpha-synuclein in its oligomeric forms, effectively preventing further aggregation into fibrils. This approach holds great promise in studying the oligomeric state of alpha synuclein and exploring potential therapeutic interventions to disrupt the progression of synucleinopathies.

Parkinson’s-associated pSer129 pathology induced in rat primary dopaminergic cells by kinetically stable alpha synuclein oligomers (cat#SPR-484).

Alpha Synuclein Monomers

StressMarq offers alpha synuclein monomers that possess the inherent ability to undergo aggregation. These monomers do not exhibit neurodegenerative activity on their own. They serve as essential components for studying the aggregation process and investigating the factors that contribute to the pathogenesis of neurodegenerative diseases associated with alpha synuclein. Researchers can utilize StressMarq’s alpha synuclein monomers to explore the molecular mechanisms underlying aggregation and to develop strategies aimed at modulating this process for potential therapeutic interventions.

For more information on the range of alpha synuclein constructs please contact StressMarq Biosciences today or browse the full catalog here:

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