Technical Data
S9500-03
Synuclein, alpha (SNCA, 127750, P37840, MGC110988, NACP, PARK1, PARK4, non-A beta Component of AD Amyloid, NACP, Parkinson Disease Familial 1, PD1)
Description:
Alpha Synuclein is a small (140-amino acid) cytoplasmic protein of unclear function that is enriched in presynaptic terminals and is the precursor protein of a nonamyloid beta component of senile plaques in Alzeheimer's Disease (AD). alpha -Synuclein is located predominantly in the presynaptic nerve terminals in the brain but is also found in low concentrations in all tissues except liver. Recent studies have shown that abnormal aggregation and accumulation of synaptic proteins, including alpha-Synuclein might be associated with plaque formation in AD and seems to be a major component of Lewy bodies in dementia with Lewy bodies (DLB). It has also been identified in the Glial Cytoplasmic Inclusions (GCIs) found in Multiple System Atrophy (MSA).

Alpha Synuclein may be involved in the regulation of dopamine release and transport. Soluble protein, normally localized primarily at the presynaptic region of axons, which can form filamentous aggregates that are the major non amyloid component of intracellular inclusions in several neurodegenerative diseases (synucleinopathies). Induces fibrillization of microtubule- associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase 3 activation.

Size 140 amino acids; 14460D

Subunit: Soluble monomer which can form filamentous aggregates. Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones.

Cellular Localization: Cytoplasm. Membrane. Nucleus. Note=Membrane- bound in dopaminergic neurons. Also found in the nucleus.

Tissue Specificity Expressed principally in brain but is also expressed in low concentrations in all tissues examined except in liver. Concentrated in presynaptic nerve terminals.

Domain: SwissProt: P37840 The NAC domain is involved in the fibril formation. The middle region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments.

PTM: Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress. & Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers. & Ubiquitinated. The predominant conjugate is the diubiquitinated form (By similarity).

Disease: SwissProt P37840. Defects in SNCA are a cause of autosomal dominant Parkinson disease 1 (PARK1) [MIM:168601, 168600]. Parkinson disease (PD) is a complex, multifactorial disorder that typically manifests after the age of 50 years, although early-onset cases (before 50 years) are known. PD generally arises as a sporadic condition but is occasionally inherited as a simple mendelian trait. Although sporadic and familial PD are very similar, inherited forms of the disease usually begin at earlier ages and are associated with atypical clinical features. PD is characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. & Defects in SNCA are the cause of Parkinson disease 4 (PARK4) [MIM:605543, 168600]. & Defects in SNCA are the cause of Lewy body dementia (DLB) [MIM:127750]. DLB is a neurodegenerative disorder clinically characterized by dementia and parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Presence of Lewy bodies are the only essential pathologic features. & Deposition of fibrillar amyloid proteins intraneuronally as neurofibrillary tangles is characteristic of Alzheimer disease (AD). SNCA is a minor protein found within these deposits, but a major non amyloid component. & Brain iron accumulation type 1 (NBIA1, also called Hallervorden-Spatz syndrome), a rare neuroaxonal dystrophy, is histologically characterized by axonal spheroids, iron deposition, Lewy body (LB)-like intraneuronal inclusions, glial inclusions and neurofibrillary tangles. SNCA is found in LB-like inclusions, glial inclusions and spheroids.

Molecular Weight: 14-19kD

Positive Control: Brain tissue

Applications:
Suitable for use in Western Blot and Immunohistochemistry. Other applications have not been tested.

Recommended Dilution:
Western Blot: 1:1000-1:2000
Immunohistochemistry (paraffin sections): 1:1000-1:2000
Immunohistochemistry (frozen sections): 1:4000-1:12,000
Optimal dilutions to be determined by the researcher.

Storage and Stability:
Lyophilized powder may be stored at 4C for short-term only. Reconstitute to nominal volume by adding sterile 40-50% glycerol and store at -20C. Reconstituted product is stable for 12 months at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
TypeIsotypeCloneGrade
PabIgGAffinity Purified
SizeStorageShippingSourceHost
20ug4C (-20C Glycerol)Blue IceHumanRabbit
Concentration:
~1mg/ml
Immunogen:
Human alpha-synuclein residue 111-131 coupled to KLH. The peptide sequence is N-GILEDMPVDPDNEAYEMPSEEC-C. This peptide is available for use in blocking studies.
Purity:
Purified by immunoaffinity chromatography.
Form
Supplied as a lyophilized powder containing no preservatives. Reconstitute with 20ul of sterile distilled water. Centrifuge to remove any residue.
Specificity:
Recognizes alpha-synuclein. The immunizing peptide was chosen to reduce crossreactivity with beta-synuclein to a minimum. Immunohistochemical and Western blot analysis of human brain indicates a high level of specificity. Species Crossreactivity: Human and rat.
Intended for research use only. Not for use in human, therapeutic, or diagnostic applications.
1. Iwai, A, et al., Neuron (1995) 14:467475. 2. Spillantini, MG, Nature (1997) 388:839840. 3. Gai, WP, et al., Lancet (1998) 352(9127):547548. 4. Abeliovich, A, et al., Neuron (2000) 25:239252.