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    1. Neuroscience

    Subthalamic, not striatal, activity correlates with basal ganglia downstream activity in normal and parkinsonian monkeys

    Marc Deffains et al.
    The spiking activity of the subthalamic nucleus, rather than the activity of striatal projection neurons, orchestrates basal ganglia downstream activity and output commands in health and Parkinson’s disease.
    1. Cell Biology
    2. Neuroscience

    MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin

    Jina Yun et al.
    By reducing mitochondrial fusion, MUL1 compensates for the mutations in PINK1 or parkin that underlie certain cases of Parkinson's disease.
    1. Cell Biology

    Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy

    Gian-Luca McLelland et al.
    A crucial step during the mitophagy cascade involves the disassembly of connections between mitochondria and the endoplasmic reticulum via the retrotranslocation of Mfn2 tethering complexes by the Parkinson's disease genes PARKIN and PINK1, as well as the ATPase VCP/p97.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Cryo-EM structure of alpha-synuclein fibrils

    Ricardo Guerrero-Ferreira et al.
    The alpha-synuclein fibril structure reported here buries residues 50-57 at the interface between its two protofilaments, suggesting that familial Parkinson's disease associated mutations in these residues lead to a structure not compatible with the one presented here.
    1. Chromosomes and Gene Expression
    2. Neuroscience

    Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice

    Mattia Volta et al.
    LRRK2 G2019S knock-in mice are a genetically faithful model that recapitulates the slow disease progression of familial PD, with initial alterations to behaviour and neurotransmission providing early pathophysiological targets for neuroprotective interventions.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Native α-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2

    Jiajie Diao et al.
    Experiments on synthetic models of synaptic vesicles have shed new light on the role of the protein α-synuclein in the central nervous system.
    1. Neuroscience

    Task-induced functional brain connectivity mediates the relationship between striatal D2/3 receptors and working memory

    Matthew M Nour et al.
    Striatal dopamine 2/3 receptor (D2/3R) availability is related to working memory-induced functional connectivity changes in the default mode network, and this mediates the relationship between D2/3Rs and task performance.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    An engineered monomer binding-protein for α-synuclein efficiently inhibits the proliferation of amyloid fibrils

    Emil Dandanell Agerschou et al.
    The high affinity α-synuclein-monomer binder AS69 converts into a strong sub-stoichiometric inhibitor of nucleation processes upon formation of the AS69-α-synuclein complex, achieving reduced aggregation in vitro and in vivo.
    1. Neuroscience

    TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau

    Maxime WC Rousseaux et al.
    Convergent screens targeting the levels of alpha-synuclein and tau identify TRIM28 as a driver of their stability, nuclear accumulation and subsequent toxicity.
    1. Cell Biology
    2. Human Biology and Medicine

    Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila

    Tom Cornelissen et al.
    Mitophagy occurs in Drosophila flight muscle and dopaminergic neurons in vivo and increases with aging in a PINK1/parkin-dependent fashion.