View source for 10xu


==Structure of amplified aSyn filament by using seed amplification assay (SAA) from MSA patient CSF.==
<StructureSection load='10xu' size='340' side='right'caption='[[10xu]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[10xu]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=10XU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=10XU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.18&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=10xu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=10xu OCA], [https://pdbe.org/10xu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=10xu RCSB], [https://www.ebi.ac.uk/pdbsum/10xu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=10xu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] Note=Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.  Defects in SNCA are the cause of Parkinson disease type 1 (PARK1) [MIM:[https://omim.org/entry/168601 168601]. A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia. The pathology of Parkinson disease 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. The disease is progressive and usually manifests after the age of 50 years, although early-onset cases (before 50 years) are known. The majority of the cases are sporadic suggesting a multifactorial etiology based on environmental and genetic factors. However, some patients present with a positive family history for the disease. Familial forms of the disease usually begin at earlier ages and are associated with atypical clinical features.<ref>PMID:9197268</ref> <ref>PMID:9462735</ref> <ref>PMID:14755719</ref>   Defects in SNCA are the cause of Parkinson disease type 4 (PARK4) [MIM:[https://omim.org/entry/605543 605543]. A complex neurodegenerative disorder with manifestations ranging from typical Parkinson disease to dementia with Lewy bodies. Clinical features include parkinsonian symptoms (tremor, rigidity, postural instability and bradykinesia), dementia, diffuse Lewy body pathology, autonomic dysfunction, hallucinations and paranoia.  Defects in SNCA are the cause of dementia Lewy body (DLB) [MIM:[https://omim.org/entry/127750 127750]. A neurodegenerative disorder clinically characterized by mental impairment leading to dementia, parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Brainstem or cortical intraneuronal accumulations of aggregated proteins (Lewy bodies) are the only essential pathologic features. Patients may also have hippocampal and neocortical senile plaques, sometimes in sufficient number to fulfill the diagnostic criteria for Alzheimer disease.
== Function ==
[https://www.uniprot.org/uniprot/SYUA_HUMAN SYUA_HUMAN] May be involved in the regulation of dopamine release and transport. Induces fibrillization of microtubule-associated protein tau. Reduces neuronal responsiveness to various apoptotic stimuli, leading to a decreased caspase-3 activation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Parkinson's disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by the misfolding and aggregation of alpha-synuclein (alphaSyn). Compelling evidence showed that alphaSyn aggregates exist as distinct conformational strains in different synucleinopathies. Recently, we reported that the alphaSyn Seed Amplification Assay (alphaSyn-SAA) can amplify and distinguish alphaSyn strains from PD and MSA. In this study, we investigate whether MSA-seeded, SAA-amplified alphaSyn fibrils retain the biological and structural properties of the alphaSyn seeds present in MSA brains. We study the biological activities of both brain-derived and SAA-amplified alphaSyn aggregates using an alphaSyn "biosensor" cell model and a synucleinopathy transmission mouse model. Our in vitro and in vivo findings reveal that the SAA-amplified alphaSyn fibrils preserve the biological properties of the brain-derived MSA strain. Detailed analyses of the in vivo studies demonstrate that both brain-derived and SAA-generated alphaSyn aggregates induce a similar disease, with comparable incubation periods, neuropathological damages and clinical manifestations. High-resolution cryo-EM analysis of SAA-amplified alphaSyn fibrils demonstrates that their conformation at the protofilament level closely resembles one of the alphaSyn filaments previously identified in MSA patient brains. Our findings suggest that SAA can amplify disease-specific misfolded alphaSyn conformation while preserving its main biological properties.

Seed amplification of MSA alpha-synuclein aggregates preserves the biological and structural properties of brain-derived aggregates.,Wang F, Banerjee V, Barria C, Ramirez S, Allison T, Gorski D, Evans H, Nguyen Q, Harrison D, Al-Lahham R, De Gregorio Carbonell N, Pinho M, Kaalund S, Folke J, Aznar S, Concha-Marambio L, Ishtikhar M, Mallampalli VK, Pritzkow S, Shahnawaz M, Baker ML, Serysheva I, Soto C Nat Commun. 2025 Dec 10;16(1):11266. doi: 10.1038/s41467-025-66146-4. PMID:41372188<ref>PMID:41372188</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 10xu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baker ML]]
[[Category: Banerjee V]]
[[Category: Serysheva II]]
[[Category: Soto C]]
[[Category: Wang F]]