Neuroscience
- Septins tune lipid kinase activity and PI(4,5)P2 turnover during G-protein–coupled PLC signalling in vivo
In 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 edema
We 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 model
RNA 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 autophagy
GPCRs 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 cochlea
The 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 axonogenesis
Tumor 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 mice
This 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.
- INPP5K and Atlastin-1 maintain the nonuniform distribution of ER–plasma membrane contacts in neurons
CIL-1 and ATLN-1 maintain the balance between ER tubules and sheets and prevent invasion of cortical ER sheets into the axon, contributing to the non-uniform distribution of neuronal ER-PM contacts.
- Choroid plexus APP regulates adult brain proliferation and animal behavior
Adult mouse choroid plexus shows elevated APP expression. sAPPα secreted into the CSF modulates neurogenic niche proliferation, whereas choroid plexus expression of fAD APP mutants leads to reduced niche proliferation, deficits in hippocampus synaptic plasticity, and learning defects.
- Biallelic ADPRHL2 mutations in complex neuropathy affect ADP ribosylation and DNA damage response
This work studies known and new ADPRHL2 mutations with different disease mechanisms overall indicating that loss of nuclear ARH3 alone is pathogenic via dysregulated nuclear ADP ribosylation.