Neuroscience
C9ORF72-derived poly-GA DPRs undergo endocytic uptake in iAstrocytes and spread to motor neuronsExtracellularly delivered poly-GAs are internalised into astrocytes via an endocytosis-dependent pathway and then spread to motor neurons, implying non-cell autonomous mechanisms in C9ORF72-ALS/FTD.
Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in miceThis longitudinal study revealed stable expression of the fast-gating channelrhodopsin f-Chrimson in cochlear neurons of mice over at least 2 yr upon a single postnatal AAV dosing of the cochlea.
SMN-deficient cells exhibit increased ribosomal DNA damageSMN deficiency leads to elevated ribosomal DNA damage that results in impaired ribosomal RNA synthesis and translation and is accompanied by a motor neuron-specific down-regulation of DDX21 protein.
Septins tune lipid kinase activity and PI(4,5)P2 turnover during G-protein–coupled PLC signalling in vivoIn Drosophila photoreceptors, PI(4,5)P2 synthesis during PLC signalling is regulated by PIP5K and septins.
Transcellular blood–brain barrier disruption in malaria-induced reversible brain edemaWe present how reversible edema can reliably be induced in experimental cerebral malaria and show that it is associated with transcellular blood–brain barrier disruption and delayed microhemorrhages.
Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse modelRNA aptamers designed to block AMPA receptors effectively reduce progression of motor dysfunction, improve TDP-43 pathology, and prevent death of motor neurons in AR2 mice, a mouse model of sporadic ALS, without adverse effects.
β-arrestin1 promotes tauopathy by transducing GPCR signaling, disrupting microtubules and autophagyGPCRs regulator, β-arrestin1, is increased in FTLD-tau patients, is required for β2-adrenergic receptor and metabotropic glutamate receptor 2-induced tau phosphorylation, promotes tau aggregation by impairing autophagy, and destabilizes microtubule dynamics, whereas genetic reduction in β-arrestin1 mitigates tauopathy and cognitive impairments.
MANF supports the inner hair cell synapse and the outer hair cell stereocilia bundle in the cochleaThe authors show in the mouse how the auditory hair cell structural maintenance is perturbed by the inactivation of Manf and the concomitant ER stress, causing early-onset, progressive hearing loss.
TGFβ-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesisTumor axonogenesis is an emerging hallmark of cancer and TGF-beta is a well-known cytokine involved in the control of cancer progression. In this study we identify a novel function for the TGF-beta signaling in cancer aggressivity by promoting cancer axonogenesis.
A brain-specific pgc1α fusion transcript affects gene expression and behavioural outcomes in miceThis study shows that loss of a brain-specific fusion isoform of PGC1a leads to up-regulation of genes and motor impairments in mice, suggesting functional differences between PGC1 isoforms in the brain.