StressMarq Biosciences has developed an extensive range of fibrillar, oligomeric and monomeric protein preparations for use in neurodegenerative disease research including alpha synuclein, beta synuclein, gamma synuclein, tau, amyloid beta, SOD1 and TTR. Our goal is to be the world leader in the development and supply of active, pathology-inducing protein aggregates to assist scientists with disease model development and accelerate neurodegenerative disease drug discovery.

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

Alpha synuclein is a highly soluble, small protein without intrinsic structure, abundantly present in the brain, primarily in presynaptic terminals of neurons. It is involved in synaptic vesicle release for signaling, including dopamine, which is important for movement.  Alpha synuclein has been shown to aggregate into various oligomeric and fibrillary forms and soluble, misfolded alpha synuclein aggregates are neurotoxic and can spread disease in a prion-like fashion. “Synucleinopathies” are a group of neurodegenerative diseases that includes Parkinson’s disease (PD), dementia with Lewy bodies (DLB), diffuse Lewy body disease (DLBD), and multiple system atrophy (MSA), which are all caused by misfolded alpha synuclein. Indeed, alpha synuclein aggregation is a hallmark of Parkinson’s disease and different forms of the protein can be used to develop disease models that reproduce the pathological features of this disorder.

StressMarq offers a wide variety of monomeric, oligomeric and fibrillar alpha synuclein constructs for neurodegenerative disease research. These preparations have different characteristics and properties. Watch our video to learn how our alpha synuclein products can assist scientists to develop disease models and test drug candidates.

Alpha Synuclein Pre-formed Fibrils (PFFs)

StressMarq’s alpha synuclein pre-formed fibrils (PFFs) seed the formation of new fibrils from active alpha synuclein monomers, and can be used to induce endogenous alpha synuclein phosphorylation and subsequent Lewy body inclusion formation in neuronal cell culture or for in vitro oligomerization studies.

Product List | PFFs

Alpha Synuclein & Tau Co-Polymer Fibrils (Mixed Fibrils/PFFs)

StressMarq’s co-polymer fibrils are developed by co-incubating monomers together to form fibrils that contain both tau and alpha synuclein proteins within a single fibril. These co-polymer fibrils have been demonstrated to seed fibril formation of both alpha synuclein monomers and of a mixture of alpha synuclein and tau monomers.

Product List | Co-Polymer Fibrils

Alpha Synuclein Oligomers 

Alpha synuclein oligomers are increasingly thought to be the toxic species in synucleinopathies. StressMarq’s kinetically stable alpha synuclein oligomers are toxic to dopaminergic neurons and induce phosphorylation of alpha synuclein Ser129 (a pathology associated with Parkinson’s disease), and are generated without the addition of any inducers or inhibitors.  StressMarq also offers dopamine-stabilized alpha synuclein oligomers and EGCG-stabilized alpha synuclein oligomers. Dopamine and EGCG can be used to stabilize alpha synuclein in its oligomeric forms, preventing further aggregation into fibrils.

Product List | Oligomers

Alpha Synuclein Monomers 

StressMarq’s alpha synuclein monomers are capable of aggregation. They do not show neurodegenerative activity.

Product List | Monomers

Selected Scientific & Product Information

3D Whole-Brain Imaging of Alpha Synuclein Aggregation Following Pre-formed Fibril (PFF) Injection

In collaboration with Gubra, StressMarq’s Alpha Synuclein PFFs (catalog#SPR-324) were injected into a mouse brain to generate a 3D whole-brain light sheet fluorescence imaging model, depicting alpha synuclein pSer129+ aggregation (shown in magenta) 4 weeks post -injection.

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Cell-to-Cell Transmission of Alpha Synuclein Pre-formed Fibrils (PFFs)

StressMarq’s Alpha Synuclein PFFs catalog#SPR-322 (below in red), 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: StressMarq’s α-syn PFFs-555 | Purple: Tubulin

Secondary Structure of Alpha Synuclein Monomers, Oligomers and Pre-formed Fibrils (PFFs)

Oligomers & Fibrils. UV-CD data suggests that StressMarq’s alpha synuclein oligomers have distinct secondary structure differences compared to our monomers and fibrils. More specifically, our Kinetically Stable Alpha Synuclein Oligomers (cat#SPR-484) show a significantly higher alpha helix content and lower beta sheet/turn content than our Alpha Synuclein Pre-formed Fibrils (Type 1) (cat#SPR-322). Alpha Synuclein Monomers (cat#SPR-316) show a strong negative signal at 200 nm, indicative of a disordered protein state (low secondary structure content).

Αlpha Synuclein Oligomers Have Distinct Secondary Structure Differences Compared to Fibrils.

Type 1 & Type 2 Pre-formed Fibrils. UV-CD data suggests StressMarq’s Alpha Synuclein Pre-formed Fibrils (PFFs), Type 1 (cat#SPR-322) and Type 2 (cat#SPR-317) both have a high beta sheet/turn content, yet do have small secondary structure differences. Alpha Synuclein Monomers (cat#SPR-316) show a strong negative signal at 200 nm indicative of a disordered protein state (low secondary structure content). For this experiment, pre-formed fibrils (PFFs) were subjected to 10 cycles of sonication prior to UV-CD to ensure solubility prior to measurement.

Alpha Synuclein Pre-formed Fibrils (PFFs), Type 1 (cat#SPR-322) and Type 2 (cat#SPR-317) have small secondary structure differences.

Kinetically Stable Alpha Synuclein Oligomers Induce Toxicity & Pathology

Kinetically Stable Alpha Synuclein Oligomers (catalog#SPR-484) are toxic to dopaminergic neurons and induce phosphorylation of alpha synuclein Ser129, a pathology associated with Parkinson’s disease.  They are stable after a freeze-thaw cycle and when incubated at 37 degrees celsius for 2 weeks.

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

Kinetically stable alpha synuclein oligomers (cat#SPR-484) show toxicity to rat primary dopaminergic neurons.

Kinetically stable alpha synuclein oligomers (cat#SPR-484) are stable after a freeze-thaw cycle and when incubated at 37 oC for 2 weeks.

Product Citations

StressMarq’s proteins for neurodegenerative disease research have been cited in many peer-reviewed scientific journals. Below is a list of the most recent product citations for our alpha synuclein proteins. A complete list of citations for alpha synuclein proteins can be seen here.

Most Recent Alpha Synuclein Citations

• From literature identification to efficient validation of targets – effects on alpha-synuclein aggregation in cortical neurons. Orrhult, L.S. et al. SfN 2024 [PSTR329.07]. 2024.
  • Catalog# SPR-324: Mouse Recombinant Alpha Synuclein Pre-formed Fibrils (Type 1)

• High-molecular-weight oligomer tau (HMWoTau) species are dramatically increased in Braak-stage dependent manner in the frontal lobe of human brains, demonstrated by a novel oligomer Tau ELISA with a mouse monoclonal antibody (APNmAb005). Fukumoto, H. et al. FASEB J. 2024.
  • Catalog# SPR-322: Human Recombinant Alpha Synuclein Pre-formed Fibrils (Type 1)
  • Catalog# SPR-484: Human Recombinant Alpha Synuclein Oligomers (Kinetically Stable)

• Exploring the potential of biomimetic peptides in targeting fibrillar and filamentous alpha-synuclein — An in silico and experimental approach to Parkinson’s disease. Frantzeskos, S. A. et al. Biomimetics. 2024.
  • Catalog# SPR-322: Human Recombinant Alpha Synuclein Pre-formed Fibrils (Type 1)

• A brain-shuttled antibody targeting alpha synuclein aggregates for the treatment of synucleinopathies. An, S. et al. bioRxiv [Preprint]. 2024.
  • Catalog# SPR-321: Human Recombinant Alpha Synuclein Monomers (Type 1)
  • Catalog# SPR-322: Human Recombinant Alpha Synuclein Pre-formed Fibrils (Type 1)
  • Catalog# SPR-322-A594: Human Recombinant Alpha Synuclein Pre-formed Fibrils: ATTO 594 (Type 1)
  • Catalog# SPR-326: Human Recombinant A53T Mutant Alpha Synuclein Pre-formed Fibrils (Type 1)

Supplemental Learning Materials

Technical Support Resources

• Handling Instructions | Synucleins
• Protocols | Alpha Synuclein
• Sonication Protocol | PFFs
• Frequently Asked Questions | Neuro Proteins

Selected Media from the StressMarq YouTube Channel

• Video | Alpha Synuclein Pre-formed Fibrils (PFFs) and Oligomers for Modelling Parkinson’s Disease
• Webinar | Protein Constructs for Neurodegenerative Disease Research | Presented by Dr. Jacob McPhail, Lead R&D Scientist, StressMarq
• Open Theatre | Alpha Synuclein Sonication | Presented Dr. Ariel Louwrier, CEO & President, StressMarq

Selected Articles from the StressMarq Blog 

• Alpha Synuclein Fibrillar Constructs | Learn about Type 1 & 2 PFFs, key mutations in PD pathology, and monomeric, fibrillar & oligomeric alpha synuclein.
• Novel Vaccine Strategies for Parkinson’s Disease | An alpha synuclein-specific epitope vaccine was observed to ameliorate motor symptoms of PD in mice.
• C-Terminally Truncated Alpha Synuclein in Human Erythrocytes | Truncation at the C-terminal of human erythrocyte alpha synuclein is associated with PD pathology.
• CDK14 Inhibition Decreases Alpha Synuclein Neurotoxicity | Genetic & pharmacological reduction of CDK14 reduces alpha synuclein pathology in PD models.

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