Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease (PD). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, eLife 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component (NAC) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial PD mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability.
Source: eLife - Category: Biomedical Science Tags: Neuroscience Structural Biology and Molecular Biophysics Source Type: research

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Publication date: Available online 27 January 2020Source: The Lancet NeurologyAuthor(s): Franziska Hopfner, Günter U Höglinger, Gregor Kuhlenbäumer, Anton Pottegård, Mette Wod, Kaare Christensen, Caroline M Tanner, Günther DeuschlSummaryBackgroundβ-adrenoceptors are widely expressed in different human organs, mediate important body functions and are targeted by medications for various diseases (such as coronary heart disease and heart attack) and many β-adrenoceptor acting drugs are listed on the WHO Model List of Essential Medicines. β-adrenoceptor antagonists are used by billions ...
Source: The Lancet Neurology - Category: Neurology Source Type: research
We present a neurobiologically plausible elaboration of an existing schema-based cognitive model of action selection in which the basal ganglia implements an activation-based selection process that mediates between assumed cortical representations of rule-based schemas. More specifically, the model employs a network of basal ganglia units with computations performed by individual BG nuclei, embedded in a corticothalamic loop that disinhibits schemas according to the received feedback. We provide bridging assumptions for linking the operation of the model with ERP components that describe the error-related negativity (ERN) ...
Source: Neuropsychologia - Category: Neurology Source Type: research
Condition:   Parkinson Disease Interventions:   Other: 11C-UCB-J PET-CT;   Other: 18F-PE2I PET-MR Sponsor:   Universitaire Ziekenhuizen Leuven Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
Source: Neuropsychiatric Disease and Treatment - Category: Psychiatry Tags: Neuropsychiatric Disease and Treatment Source Type: research
This study was registered with the Chinese Clinical Trial Registry under ChiCTR-TRC-14004707. Registered on May 27, 2014.
Source: Frontiers in Neurology - Category: Neurology Source Type: research
The spinal cord stimulation (SCS) market growth should improve in 2020 as leaders in the space launch new products and benefit from recent acquisitions and invest in potential indication expansions, according to Needham &Co.'s Mike Matson. The medtech analyst published a report Monday sharing his takeaways from the North American Neuromodulation Society (NANS) meeting in Las Vegas, NV over the weekend. Matson noted that SCS device market growth should continue to improve in 2020 and beyond, thanks to a number of factors. The analyst estimates that SCS currently represents about $2.5 billion, whi...
Source: MDDI - Category: Medical Devices Authors: Tags: Business Source Type: news
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Source: mobihealthnews - Category: Information Technology Source Type: news
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Source: the Mail online | Health - Category: Consumer Health News Source Type: news
(Rutgers University) A collaboration between scientists at Rutgers University and Scripps Research leads to the discovery of a small molecule that may slow down or stop the progression of Parkinson's disease
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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