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Three Research Tools for Neurodegenerative Diseases

Published On 02/13/2023 1:59 PM
Three active, pathology-inducing proteins for drug discovery and model development in neurodegenerative diseases

Neurodegeneration disease is an umbrella term for a broad group of progressive neurological disorders that are characterized by neurons becoming damaged or dying. As neurons do not readily reproduce, these diseases of the nervous system are debilitating and incurable.

Neurodegenerative diseases can impair movement (ataxia) or mental functioning (dementia). The risk for acquiring a neurodegenerative disease increases with age due to heightened levels of oxidative stress and DNA mutations. Neurodegenerative disease includes Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Friedreich’s ataxia, Huntington’s disease (HD), Lewy body dementia, etc.

AD and PD as the most common neurodegenerative disorders are both characterized by the presence of plaques in the brain – these consist of protein aggregates which include the key proteins: alpha synuclein, Amyloid beta and Tau. By using active, pathology-inducing aggregates as reagents, our scientists can develop reliable disease models and accelerate drug discovery.

1. Alpha Synuclein

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.

Biohippo carries a wide variety of monomeric, oligomeric and fibrillar alpha synuclein constructs for neurodegenerative disease research. These preparations have different characteristics and properties. 

1.1 Alpha Synuclein Pre-formed Fibrils (PFFs) 

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. Alpha Synuclein Pre-formed Fibrils (PFFs) (BHP11900142) were shown to be taken up by SH-SY5Y cells and transmitted to neuronal iPSCs within 14 days.

Alpha Synuclein Pre-formed Fibrils (PFFs) 


Human Alpha Synuclein Pre-formed Fibrils (Type 1)


Human Alpha Synuclein Pre-formed Fibrils (ATTO 594 conjugated, Type 1)


Mouse Alpha Synuclein Pre-formed Fibrils (Type 1)


Human Alpha Synuclein Pre-formed Fibrils (Type 2)


Human Alpha Synuclein N-Terminal Acetylated Pre-formed Fibrils (Type 1)


Human Alpha Synuclein A53T Mutant Pre-formed Fibrils (Type 1)


Rat Alpha Synuclein Pre-formed Fibrils


Human Alpha Synuclein Filaments (Immature Fibrils)


 Blue: Hoechst/DNA | Green: SHSY5Y-GFP | Red: StressMarq’s α-syn PFFs-555 | Purple: Tubulin
Picture 1: Blue: Hoechst/DNA | Green: SHSY5Y-GFP | Red: StressMarq’s α-syn PFFs-555 | Purple: Tubulin

1.2 Alpha Synuclein Oligomers 

Alpha synuclein oligomers are increasingly thought to be the toxic species in synucleinopathies. Kinetically stable alpha synuclein oligomers (BHP11901215) 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.  We also carry dopamine-stabilized alpha synuclein oligomers (BHP11901184) and EGCG-stabilized alpha synuclein oligomers (BHP11901187). Dopamine and EGCG can be used to stabilize alpha synuclein in its oligomeric forms, preventing further aggregation into fibrils.

Alpha Synuclein Oligomers


Human Alpha Synuclein Oligomers (Kinetically Stable)


Human Alpha Synuclein Oligomers (Dopamine HCl Stabilized)


Human Alpha Synuclein Oligomers (EGCG Stabilized)


1.3 Alpha Synuclein Monomers

Alpha synuclein monomers are capable of aggregation and do not show neurodegenerative activity.
Alpha Synuclein Monomers  SKU
Human Alpha Synuclein Monomers (Type 1) BHP11900139
Human Alpha Synuclein Monomers (Type 2) BHP11900124
Mouse Alpha Synuclein Monomers (Type 1) BHP11900145
Human Alpha Synuclein A53T Mutant Monomers (Type 1) BHP11900163
Human Alpha Synuclein N-Terminal Acetylated Monomers (Type 1) BHP11901121
Rat Alpha Synuclein Monomers BHP11901213

2. Amyloid Beta

In the brain, amyloid beta peptide (Aβ) is generated by protease cleavage of amyloid precursor protein (APP), which aggregates into oligomers, protofibrils, fibrils and ultimately plaques in neurodegenerative diseases. The accumulation of Aβ plaques in the brain is considered a hallmark of Alzheimer’s disease (AD), and most of the drugs tested for AD in the past 20 years have targeted amyloid beta accumulation. Soluble Aβ oligomers isolated from the brains of AD patients or those generated in vitro potently impaired synapse structure and function.  Aβ oligomers generated in vitro were toxic to PC12 cells and SH-SY5Y cells. Aβ was demonstrated to interact with tauopathies to affect neurodegeneration in AD patients and accumulations of Aβ were shown to be associated with lower survival rates in Parkinson’s disease patients with dementia.
Amyloid Beta SKU
Human Amyloid Beta 1-42 Pre-formed Fibrils (PFFs) BHP11901217
Human Amyloid Beta 1-42 Oligomers BHP11901218
Human Amyloid Beta 1-42 Peptide (HFIP, monomeric) BHP11901216

3. Tau Pre-formed Fibrils (PFFs), Filaments, & Monomers 

Active tau proteins can be used to study tau aggregation, a hallmark of neurodegenerative diseases including Alzheimer’s. The process of tau aggregation can be seeded by active tau PFFs, which recruit monomers to form larger tau fibrils.  This has been demonstrated in thioflavin T assays where an increase in fluorescence – indicative of tau fibrillization – is seen when active tau PFFs are combined with active tau monomers.  Certain tau PFF have been injected into P301L mice, where they seed tau aggregation and induce tau pathology in the hippocampus (Picture 2).

3.1 Tau Pre-formed Fibrils (PFFs)

Tau Pre-formed Fibrils (PFFs)


Human Tau-441 (2N4R) Wild-Type Pre-formed Fibrils 


Human Tau-441 (2N4R) P301S Mutant Pre-formed Fibrils 


Human Tau-441 (2N4R) P301S Mutant Pre-formed Fibrils: ATTO 488 


Human Tau-441 (2N4R) P301S Mutant Pre-formed Fibrils (Baculovirus/Sf9) 


Mouse Tau-441 (2N4R) P301S Mutant Pre-formed Fibrils 


Human Tau-441 (2N4R) P301S Mutant Filaments 


Human Tau Truncated Fragment (AA297-391) (dGAE) Pre-formed Fibrils 


Human Tau Truncated (AA297-391) (dGAE C322A) Pre-formed Fibrils 


Human Tau (K18) P301L Mutant Pre-formed Fibrils 


Human Tau (K18) Delta K280 Mutant Pre-formed Fibrils 


 Immunohistochemistry analysis of P301L mouse hippocampus injected with K18 P301L tau PFFs (BHP11900160) shows seeding of tau pathology at injection site nine weeks post-injection. AT8 (pSer202/pThr205) tau antibody shows tangle-like inclusions. Inset: negative control. Experiments performed at reMYND N.V.

Picture 2: Immunohistochemistry analysis of P301L mouse hippocampus injected with K18 P301L tau PFFs (BHP11900160) shows seeding of tau pathology at injection site nine weeks post-injection. AT8 (pSer202/pThr205) tau antibody shows tangle-like inclusions. Inset: negative control. Experiments performed at reMYND N.V.

3.2 Tau Monomers

Tau Monomers


Human Tau-441 (2N4R) Wild-Type Monomers


Human Tau-441 (2N4R) P301S Mutant Monomers


Human Tau-441 (2N4R) P301S Mutant Monomers (Sf9/Baculovirus) 


Mouse Tau-441 (2N4R) P301S Mutant Monomers


Human Tau Truncated Fragment (AA297-391) (dGAE) Monomers


Human Tau Truncated Fragment (AA297-391) (dGAE C322A) Monomers


Human Tau (K18) P301L Mutant Monomers


Human Tau (K18) Delta K280 Mutant Monomers



All the above products are available at Biohippo. Our supplier, StressMarq, is the only commercial company with a wide and validated PPF/oligomer portfolio. If you have any questions, please feel free to contact us at [email protected]. For more information, please visit our website:

This entry was posted in Product Literature