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: - 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
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Source: Frontiers in Neurology - Category: Neurology Source Type: research
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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
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Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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