Journal: medRxiv / Year: 2025 Title: A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features. Authors: Christof Brücke / Mohammed Al-Azzani / Nagendran Ramalingam / Maria Ramón / Rita L Sousa / Fiamma Buratti / Michael Zech / Kevin Sicking / Leslie Amaral / Ellen Gelpi / Aswathy Chandran / ...Authors: Christof Brücke / Mohammed Al-Azzani / Nagendran Ramalingam / Maria Ramón / Rita L Sousa / Fiamma Buratti / Michael Zech / Kevin Sicking / Leslie Amaral / Ellen Gelpi / Aswathy Chandran / Aishwarya Agarwal / Susana R Chaves / Claudio O Fernández / Ulf Dettmer / Janin Lautenschläger / Markus Zweckstetter / Ruben Fernandez Busnadiego / Alexander Zimprich / Tiago Fleming Outeiro / Abstract: BACKGROUND: Parkinson's disease (PD) affects millions of people worldwide, but only 5-10% of patients suffer from a monogenic form of the disease with Mendelian inheritance. , the gene encoding for ...BACKGROUND: Parkinson's disease (PD) affects millions of people worldwide, but only 5-10% of patients suffer from a monogenic form of the disease with Mendelian inheritance. , the gene encoding for the protein alpha-synuclein (aSyn), was the first to be associated with familial forms of PD and, since then, several missense variants and multiplications of the gene have been established as rare causes of autosomal dominant forms of PD. AIM AND METHODS: A patient carrying aSyn missense mutation and his family members were studied. We present the clinical features, genetic testing - whole exome sequencing (WES), and neuropathological ...AIM AND METHODS: A patient carrying aSyn missense mutation and his family members were studied. We present the clinical features, genetic testing - whole exome sequencing (WES), and neuropathological findings. The functional consequences of this aSyn variant were extensively investigated using biochemical, biophysical, and cellular assays. RESULTS: The patient exhibited a complex neurodegenerative disease that included generalized myocloni, bradykinesia, dystonia of the left arm and apraxia. WES identified a novel heterozygous variant ...RESULTS: The patient exhibited a complex neurodegenerative disease that included generalized myocloni, bradykinesia, dystonia of the left arm and apraxia. WES identified a novel heterozygous variant (cDNA 40G>A; protein G14R). Neuropathological examination showed extensive atypical aSyn pathology with frontotemporal lobar degeneration (FTLD) and nigral degeneration pattern with abundant ring-like neuronal inclusions, and few oligodendroglial inclusions. Sanger sequencing confirmed the variant in the healthy, elderly parent of the patient patient suggesting incomplete penetrance. NMR studies suggest that the G14R mutation induces a local structural alteration in aSyn, and lower thioflavin T binding in in vitro fibrillization assays. Interestingly, the G14R aSyn fibers display different fibrillar morphologies as revealed by cryo-electron microscopy. Cellular studies of the G14R variant revealed increased inclusion formation, enhanced membrane association, and impaired dynamic reversibility of serine-129 phosphorylation. SUMMARY: The atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of the variant with a distinct clinical and ...SUMMARY: The atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of the variant with a distinct clinical and pathological phenotype, which is further supported by the properties of the mutant aSyn, compatible with the strain hypothesis of proteinopathies.
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi
Movie
Controller
Open data
Basic information
Map data
Sample
Keywords
Function and homology information
Homo sapiens (human)
Authors
Germany, 
United States, 5 items 
Citation
Structure visualization
Downloads & links
emd_52166.png
http://ftp.pdbj.org/pub/emdb/structures/EMD-52166
Z (Sec.)
Y (Row.)
X (Col.)
Sample components
Escherichia coli (E. coli)
Processing
Electron microscopy
FIELD EMISSION GUN
