Neuroscience
- TrkB signaling regulates the cold-shock protein RBM3-mediated neuroprotection
The neuroprotective effects of the cold-shock protein RBM3 have broad appeal for therapy. RBM3 induction through cooling occurs through a non-canonical pattern of TrkB signaling. The pathway can now be targeted pharmacologically for RBM3-mediated neuroprotection without the need for cooling.
- TrkA-mediated endocytosis of p75-CTF prevents cholinergic neuron death upon γ-secretase inhibition
The findings shed light into the adverse effects of GSIs observed in the Alzheimer’s field and explain, at least in part, the unexpected worsening in cognition observed in the semagacestat Phase 3 trial.
- Insulin signaling mediates neurodegeneration in glioma
Tumoral cells secrete an antagonist that attenuates insulin signaling in neurons. It induces mitochondrial defects and synapse loss; restoring neuronal insulin activity rescues neurodegeneration.
- HTR6 and SSTR3 ciliary targeting relies on both IC3 loops and C-terminal tails
Ciliary accumulation of G protein–coupled receptors HTR6 and SSTR3 depends on redundant ciliary targeting sequences acting via ciliary trafficking adapters TULP3 and RABL2.
- Meningeal lymphoid structures are activated under acute and chronic spinal cord pathologies
We found that acute insult to the central nervous system induces the formation of lymphocyte aggregates reminiscent of tertiary lymphoid structures within the spinal cord meninges. Unlike draining CNS-cervical lymph nodes, meningeal lymphocytes are locally activated during neuro-inflammtion and neurodegeneration.
- Short-duration splice promoting compound enables a tunable mouse model of spinal muscular atrophy
We describe drug treatment paradigms that allow investigation of cellular and molecular pathogenesis at different stages of spinal muscular atrophy in a mouse model.
- Multiplexed chemogenetics in astrocytes and motoneurons restore blood–spinal cord barrier in ALS
Chemogenetic motoneuron excitation and astrocyte GPCR-Gi signaling restore blood–spinal cord barrier, disrupted in four ALS mouse models, revealing its role in disease progression but not initiation.
- Mitochondrial spongiotic brain disease: astrocytic stress and harmful rapamycin and ketosis effect
Astrocyte-specific mtDNA depletion causes spongiotic encephalopathy, aggravated by ketogenic diet or rapamycin. Astrocytes, but not neurons, drive mitochondrial integrated stress response in the CNS.
- Prion infection, transmission, and cytopathology modeled in a low-biohazard human cell line
Expanding the toolbox of prion research to a low-biohazard, scalable human cell model.
- Genetic targeting of neurogenic precursors in the adult forebrain ventricular epithelium
In vivo evidence for precursors that produce neurons independent of neurosphere-forming neural stem cells suggests the adult forebrain, like the developing brain, has two distinct neurogenic pathways.