Neurology

Amyloid fibrils extracted from brains of patients with frontotemporal lobar degeneration with TAR DNA-binding-protein immunoreactivity (FTLD-TDP) are made up of transmembrane protein 106B.

The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.

Crystal structures of the σ₂ receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ₂-selective ligands and providing insight into the role of σ₂ in neuropathic pain.

The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.

Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis.

Aggressive cerebral cavernous malformations (CCMs) are found to grow through a three-hit cancer-like mechanism, involving gain of function of a gene that promotes vascular growth, and loss of function of genes that suppress it.

Odorant-dependent sniff responses predicted the long-term survival rates of patients with severe brain injury, and discriminated between individuals who were unresponsive and in minimally conscious states.

Breakdown of the blood–brain barrier in individuals carrying the ε4 allele of the APOE gene, but not the ε3 allele, increases with and predicts cognitive impairment and is independent of amyloid β or tau pathology.

Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.

Single-cell RNA sequencing of cells from humans with multiple sclerosis and mice with a model of the disease identifies a population of disease-promoting astrocytes in which anti-oxidant and anti-inflammatory proteins are suppressed.

The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.

The authors show that NLRP3 inflammasome is activated in microglia of patients with fronto-temporal dementia and in a mouse model of tau pathology, and that the loss of NLRP3 inflammasome function decreases tau pathology and improves cognition in mice.

Activated clonally expanded CD4⁺ T cells display specificity to the myelin peptide MOG, whereas clonally expanded CD8⁺ T cells depend on T cell receptor recognition of unrelated surrogate peptides and have a regulatory function.

A study of the functional microbiome in a mouse model of ALS shows that several gut bacteria may modulate the severity of the disease.

Single-nucleus RNA sequencing analysis identifies different subclusters of oligodendroglia in white matter from individuals with multiple sclerosis compared with controls, and these differences may be important for understanding disease progression.

Archived vials of cadaveric human growth hormone contain substantial levels of amyloid-β (Aβ) peptides and can seed Aβ plaques in susceptible mice, suggesting that this material could have transmitted Aβ pathology to humans.

This Perspective discusses developments in LED-based solid-state lighting for physiological and agricultural applications, and the anticipated benefits in terms of health and productivity.

Dopamine in the medial prefrontal cortex modulates behavioural responses to aversive stimuli by increasing the signal-to-noise ratio of neurons projecting to the dorsal periaqueductal grey.

Spatially selective and temporally controlled stimulation of the spinal cord, together with rehabilitation, results in substantial restoration of locomotor function in humans with spinal cord injury.

Human neural stem cells from the subventricular zone are identified as the cells of origin that contain the driver mutations for glioblastomas.

The structure of huntingtin in complex with an interactor is determined to an overall resolution of 4 Å, paving the way for improved understanding of the cellular functions of this protein.

Deposition and spreading of amyloid-β pathology in mice requires binding to microglia-released ASC specks.

Braf ^V600E expression in resident macrophage progenitors leads to clonal expansion of ERK-activated microglia, which causes synaptic and neuronal loss in the brain and results in lethal neurodegenerative disease in adult mice.

Antisense oligonucleotides against ATXN2 improved motor neuron function and restored firing frequency in cerebellar Purkinje cells in mouse models of spinocerebellar ataxia type 2.

Structural differences in 40- and 42-residue-long amyloid-β fibrils seeded in vitro from the cortical tissue of patients with different clinical subtypes of Alzheimer’s disease suggest that different fibril structures form in different disease variants and with different peptide lengths.

A wireless brain–spine interface is presented that enables macaques with a spinal cord injury to regain locomotor movements of a paralysed leg.

Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allows for robust axonal regrowth only if the astrocytic scar is present—a result that questions the prevailing dogma and suggests that astrocytic scarring aids rather than prevents central nervous system axon regeneration post injury.

Deep brain stimulation (DBS) of the fimbria–fornix—a region that provides input to the hippocampus—is shown to restore hippocampus-dependent memory and hippocampal long-term potentiation and neurogenesis in a mouse model of Rett syndrome, suggesting that DBS, which is already used in the treatment of several neurological conditions, could be a viable approach to mitigating cognitive impairment in Rett syndrome and other disorders of childhood intellectual disability.