Products for Neurodegeneration Research: α-synuclein

 α-synuclein Antibodies and Kits (click catalog number for product and ordering information)

Catalog Number	Product Name	Specificity	Size
CAC-TIP-SN-P01	Anti Alpha Synuclein (Amino Acids 1-10) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P02	Anti Alpha Synuclein (Amino Acids 11-20) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P03	Anti Alpha Synuclein (Amino Acids 21-30) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P04	Anti Alpha Synuclein (Amino Acids 31-40) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P05	Anti Alpha Synuclein (Amino Acids 41-50) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P06	Anti Alpha Synuclein (Amino Acids 51-60) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P07	Anti Alpha Synuclein (Amino Acids 61-70) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P08	Anti Alpha Synuclein (Amino Acids 75-91) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-P09	Anti Alpha Synuclein (Amino Acids 131-140) pAb (Rabbit, Antiserum)	Human, Mouse	50UL
CAC-TIP-SN-SET	Anti Alpha Synuclein (9 Antibody Set) pAb (Rabbit, Antiserum)	Human, Mouse	9x10UL
CSB-E18033h	Human Alpha Synuclein (non A4 component of amyloid precursor) oligomer (SNCA oligomer) ELISA kit	Human	1x96 rxns
CSB-EL021912RA	Rat Alpha-synuclein (SNCA) ELISA kit	Rat	1x96 rxns
CSR-SYN01	Alpha Synuclein Aggregation Assay Kit	-	1 Kit
CSR-SYN03	Alpha Synuclein Fibrils	Human	0.1MG
CSR-SYN04-2	Alpha Synuclein	Human	0.1MG and 1MG
CSB-EL010868HU	Human heparan sulfate proteoglycan 2 (HSPG2) ELISA kit	Human	1x96 rxns
CSB-E14983h	Human Syndecan-1/CD138(SDC1) ELISA Kit	Human	1x96 rxns
CSB-EL020889HU	Human Syndecan-2(SDC2) ELISA kit	Human	1x96 rxns
CSB-EL020888MO	Mouse Syndecan-1(SDC1) ELISA kit	Mouse	1x96 rxns
CSB-EL020889MO	Mouse Syndecan-2(SDC2) ELISA kit	Mouse	1x96 rxns
CSB-E17413p	Pig Syndecan-1/CD138(SDC1) ELISA Kit	Pig	1x96 rxns
CSB-EL010868RA	Rat heparan sulfate proteoglycan 2 (HSPG2) ELISA kit	Rat	1x96 rxns
CSB-E17115r	Rat Syndecan-1/CD138(SDC1) ELISA Kit	Rat	1x96 rxns
CSB-EL020889RA	Rat Syndecan-2(SDC2) ELISA kit	Rat	1x96 rxns
CAC-NU-07-004	Anti Syndecan-3 (N-Syndecan/Neuroglycan) pAb (Rabbit, Antiserum)	Mouse, Rat	100UL
CSB-E11834h	human S100 calcium binding protein A9/calgranulin B,S100A9 ELISA Kit	Human	1x96 rxns
CSB-EL020642MO	Mouse Protein S100-A9(S100A9) ELISA kit	Mouse	1x96 rxns
CSB-EL020642RA	Rat Protein S100-A9(S100A9) ELISA kit	Rat	1x96 rxns
YMS-80126-EX	S100A9 Assay Kit	Rat	96 tests
YMS-80086	Anti S100A9 mAb (Clone 15E9)	Rat	200UG

Just as pathological tau protein inclusions define the Tauopathies, the synucleinopathies are neurodegenerative diseases defined by deposition of α-synuclein aggregates in neuronal and non-neuronal cells in the brain. The classic synucleinopathies are PD, dementia with Lewy bodies (DLB) and multiple systems atrophy (MSA). The defining histopathological features in PD are spindle- or thread-like Lewy neurites (LNs) in neuronal processes and globular Lewy bodies (LBs) in neuronal perikarya. Just as some APP mutations cause FAD, some mutations in SNCA (for example, E46K and A53T) are associated with familial PD. Please scroll to the ORDERING section to explore CosmoBio USA's α-synuclein reagents that have proven helpful in the study of neurodegenerative diseases.

α-Synuclein is a small 140 amino acid protein encoded by the SNCA gene on chromosome 4q22.1. It is found in many neuronal compartments and is particularly abundant in presynaptic terminals, where it may be involved in vesicle trafficking and neurotransmitter release. It is intrinsically flexible in solution and, like other intrinsically disordered proteins (IDPs), acquires structure upon binding to biological partners, including lipid membranes which appear to play a key role in α-synuclein function and dysfunction. While α-synuclein has been associated with several biological activities, including regulation of synaptic vesicle pools, neurotransmitter release, SNARE complex assembly and vesicle trafficking, its precise functions remain enigmatic and controversial.

 From: Brás, I., Dominguez‐Meijide, A., Gerhardt, E., Koss, D., Lázaro, D., Santos, P., Vasili, E., Xylaki, M., Outeiro, T. (2020). Synucleinopathies: Where we are and where we need to go Journal of Neurochemistry 153(4), 433-454.

Many factors contributing to α-synuclein aggregation are linked to its structure. α-Synuclein is composed of three distinct domains: N-terminal region contains four imperfect KTKEGV motif repeats that can fold into amphipathic helices. The central non-amyloid component domain is hydrophobic and is crucial for α-synuclein aggregation and C-terminal region is enriched in highly acidic and charged amino acids. α-Synuclein is classified as an intrinsically disordered protein that may exist as an un-structured monomer. Upon membrane/lipid binding, the N-terminal region adopts an alpha-helical structure that may promote membrane curvature. α-Synuclein mutations associated with familial PD (A30P, E46K, H50Q, G51D or A53T) are found mostly at the N-terminal helix and lead to accelerated fibrillization and increased toxicity. These mutation-mediated effects resulted from altered α-synuclein secondary structure (A30P, A53T); enhanced α-synuclein binding to phospholipids (E46K); and from formation of α-synuclein fibrils more prone to activate proapoptotic pathways (G51D).

The non-amyloid component domain of α-synuclein comprises the 35 residue (aa61-95) central hydrophobic region and plays a major role in α-synuclein oligomerization and aggregation. This hydrophobic motif may become exposed during misfolding and initiate aggregation. Mutation or deletion of this region significantly reduced α-synuclein filament assembly.

Proteolytic cleavage can alter α-synuclein structure to favor aggregation. Thus, C-terminal truncation of α-synuclein is a common post-translational modification abundant in Lewy bodies. Tissue-specific expression of C-terminally truncated α-synuclein in nigral dopaminergic neurons markedly reduced dopamine levels in a transgenic mouse model, suggesting a failure to maintain α-synuclein-regulated dopamine homeostasis.

Hyperphosphorylation of α-Synuclein impaired multiple aspects of its function. α-Synuclein phosphorylation at S129 and Y125 resulted in reduced interactions with proteins involved in the mitochondrial electron transport chain complex. At the same time these PTMs enhanced interactions with proteins involved in cytoskeletal organization, vesicular trafficking and serine phosphorylation. Not all phosphorylation promoted aggregation. For example, S87 phosphorylation, which increased the conformational flexibility of α-synuclein and lead to reduced binding affinity to lipid membranes, also reduced the potential of α-synuclein to form fibrils. These studies have been assisted by antibodies against specific phospho-epitopes that could recognize hyperphosphorylated α-synuclein in LBs.

Other pathways to accumulation of α-synuclein aggregates were indirectly promoted by oxidative stress, fatty acids (i.e., glucosylceramide) and impaired protein clearance mechanisms. Proteins with chaperone activity towards α-synuclein, such as Hsp70 and several other heat-shock proteins, and some presynaptic proteins like Munc18-1 regulated α-synuclein aggregation and toxicity. In addition, α-synuclein-interacting enzymes, such as peptidyl prolyl isomerases FKBP12, FKBP52 and PREP (prolyl oligopeptidase) promoted α-synuclein oligomerization and aggregation.

The formation and spread of α-synuclein pathology have been extensively studied using the intracerebral seeding method. Human α-synuclein, extracted from post mortem PD patient brains, was capable of seeding intracellular accumulation of phosphorylated α-synuclein in both monkeys and in WT mice, though without the formation of clear LB-like inclusions or with LB-like inclusions only present in certain brain regions such as the amygdala in about half of injected mice. Human brain-derived α-synuclein from patients with MSA or incidental LBD (Lewy body pathology without clinical symptoms of dementia or Parkinsonism) was also effective at seeding hyperphosphorylated α-synuclein pathology in transgenic mice that modestly overexpressed WT human α-synuclein in the absence of murine α-synuclein. Seeding with extracts from pathology laden brains of aged α-synuclein transgenic mice (line M83) accelerated the onset of α-synuclein pathology in young pre-symptomatic M83 hosts, much like what has been observed following seeding of appropriate hosts with Aβ or tau derived from the brains of transgenic mice. Seeded α-synuclein pathology took the form of LB- and LN-like intracellular deposits, resembling the pathology that emerges spontaneously in PD and DLB. Further, the deposits were recognized by conformation-dependent antibodies against α-synuclein and ubiquitin and were stained by the amyloidophilic dye Thioflavin S (ThS). These results resemble how, in WT hosts, tau derived from patients with AD or other Tauopathies could seed intracellular accumulation of pathological, hyperphosphorylated tau that eventually progressed to formation of insoluble aggregates, strengthening the theory that prion-like templated misfolding contributes to neurodegenerative disease-associated protein deposition.
(Adapted from: Birol, M., Melo, A. (2020). Untangling the Conformational Polymorphism of Disordered Proteins Associated With Neurodegeneration at the Single-Molecule Level Frontiers in Molecular Neuroscience 12(), 309; Valera, E., Spencer, B., Masliah, E. (2016). Immunotherapeutic Approaches Targeting Amyloid-β, α-Synuclein, and tau for the Treatment of Neurodegenerative Disorders Neurotherapeutics 13(1), 179-189; Yan, X., Uronen, R., Huttunen, H. (2018). The interaction of α-synuclein and tau: A molecular conspiracy in neurodegeneration? Seminars in Cell & Developmental Biology 99(), 55-64; McAllister, B., Lacoursiere, S., Sutherland, R., Mohajerani, M. (2020). Intracerebral seeding of amyloid-β and tau pathology in mice: factors underlying prion-like spreading and comparisons with α-synuclein Neuroscience & Biobehavioral Reviews 112(), 1-27; and Brás, I., Dominguez‐Meijide, A., Gerhardt, E., Koss, D., Lázaro, D., Santos, P., Vasili, E., Xylaki, M., Outeiro, T. (2020). Synucleinopathies: Where we are and where we need to go Journal of Neurochemistry 153(4), 433-454)