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Article
Open AccessDifferential functional consequences of GRIN2A mutations associated with schizophrenia and neurodevelopmental disorders
Human genetic studies have revealed rare missense and protein-truncating variants in GRIN2A, encoding for the GluN2A subunit of the NMDA receptors, that confer significant risk for schizophrenia (SCZ). Mutations ...
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Article
Targeting synapse function and loss for treatment of neurodegenerative diseases
Synapse dysfunction and loss are hallmarks of neurodegenerative diseases that correlate with cognitive decline. However, the mechanisms and therapeutic strategies to prevent or reverse synaptic damage remain e...
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Article
Open AccessMouse mutants in schizophrenia risk genes GRIN2A and AKAP11 show EEG abnormalities in common with schizophrenia patients
Schizophrenia is a heterogeneous psychiatric disorder with a strong genetic basis, whose etiology and pathophysiology remain poorly understood. Exome sequencing studies have uncovered rare, loss-of-function va...
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Article
Integrative in situ map** of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease
Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can...
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Article
Open AccessComplement C1q-dependent excitatory and inhibitory synapse elimination by astrocytes and microglia in Alzheimer’s disease mouse models
Microglia and complement can mediate neurodegeneration in Alzheimer’s disease (AD). By integrative multi-omics analysis, here we show that astrocytic and microglial proteins are increased in TauP301S synapse frac...
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Article
Open AccessPCDH7 interacts with GluN1 and regulates dendritic spine morphology and synaptic function
The N-terminal domain (NTD) of the GluN1 subunit (GluN1-NTD) is important for NMDA receptor structure and function, but the interacting proteins of the GluN1-NTD are not well understood. Starting with an unbia...
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Article
Publisher Correction: Global site-specific neddylation profiling reveals that NEDDylated cofilin regulates actin dynamics
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Global site-specific neddylation profiling reveals that NEDDylated cofilin regulates actin dynamics
Neddylation is the post-translational protein modification most closely related to ubiquitination. Whereas the ubiquitin-like protein NEDD8 is well studied for its role in activating cullin−RING E3 ubiquitin l...
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Article
A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci
Robert Graham and colleagues carried out a GWAS meta-analysis for Parkinson's disease (PD) and report 17 new risk loci. Their analyses support a key role for autophagy and lysosomal biology in PD risk.
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Article
Open AccessCharacterization of Social Behaviors in caspase-3 deficient mice
Impaired social interaction is a defining feature of autism spectrum disorder, a neurodevelopmental disorder that shows a strong male preponderance in prevalence. Studies have identified neural circuits, neuro...
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Article
The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy
Cells maintain healthy mitochondria by degrading damaged mitochondria through mitophagy; defective mitophagy is linked to Parkinson’s disease. Here we report that USP30, a deubiquitinase localized to mitochond...
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Article
Open AccessGluN2B Antagonism Affects Interneurons and Leads to Immediate and Persistent Changes in Synaptic Plasticity, Oscillations, and Behavior
Although antagonists to GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) have been widely considered to be neuroprotective under certain pathological conditions, their immediate and lasting impacts on sy...
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Article
Strength in numbers
A process called long-term potentiation mediates information storage — learning and memory — at the level of neurons. An in vitro study turns the molecular understanding of this process on its head. But researche...
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Article
GKAP orchestrates activity-dependent postsynaptic protein remodeling and homeostatic scaling
Ubiquitin proteasome system–mediated, neuronal activity–dependent protein turnover at synapses often occurs in an ensemble fashion where a group or groups of postsynaptic density (PSD) proteins are degraded to...
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Article
Three-dimensional imaging of solvent-cleared organs using 3DISCO
The examination of tissue histology by light microscopy is a fundamental tool for investigating the structure and function of organs under normal and disease states. Many current techniques for tissue sectioni...
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Article
Open AccessCaspases in synaptic plasticity
Caspases are a family of cysteine proteases that play key roles in programmed cell death (apoptosis). Mounting evidence in recent years shows that caspases also have important non-apoptotic functions in multip...
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Article
Open AccessNMDA receptors and BAX are essential for Aβ impairment of LTP
Accumulation of amyloid-β (Aβ) is a hallmark of Alzheimer’s disease, a neurodegenerative disorder in which synapse loss and dysfunction are early features. Acute exposure of hippocampal slices to Aβ leads to c...
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Article
Aβ1–42 inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β
Amyloid-β is known to inhibit hippocampal long-term potentiation (LTP), but the underlying molecular mechanisms are only partially understood. In this capacity, Jo and colleagues report the involvement of a si...
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Article
Muscarinic receptors induce LTD of NMDAR EPSCs via a mechanism involving hippocalcin, AP2 and PSD-95
This study finds that stimulation of muscarinic acetylcholine receptors causes long-term depression (LTD) of NMDA receptor–mediated synaptic transmission. This LTD requires the release of Ca2+ from IP3-sensitive ...
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Article
Open AccessA novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α
Long-term depression (LTD) in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs) and muscarinic acethycholin...
