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To mark the 20th anniversary of Nature Reviews Neurology, we have asked leaders of neurological societies across the world to reflect on progress over the past two decades and consider what the future holds for neurology in their region. Here, we speak to Elena Moro, President of the European Academy of Neurology.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

This trial found spinal cord stimulation was well tolerated in people with gait-impaired Parkinson’s disease. It suggests that longer use improved lower-body motor symptoms while reducing thalamic hypermetabolism and cholinergic overactivity.

Huntington’s disease is caused by mutation in the HTT gene. Here, the authors screen for suppressors of mutant HTT-induced toxicity, identifying Mtf1. Mtf1 reduced oxidative stress and cell death in stem cells, and motor defects and protein aggregates in mouse models.

Anderson localization is a regime where diffusion is inhibited, leading to the localization of waves. Here, Leonetti et al.use wavefront shaping to achieve focusing in disordered optical fibres in the Anderson regime and demonstrate efficient focusing action.

Abnormal accumulation of the RNA-binding protein FUS and mutations within the FUS gene have been found in association with amyotrophic lateral sclerosis (ALS). Here, Dini Modigliani et al.uncover a FUS regulatory circuit that implicates the microRNAs miR-141 and miR-200a in a feedback loop disrupted by an ALS-associated mutation.

Here the authors report that using an “isogenomic” reference genome (fully matched to the experimental cell line) improves the accuracy of genomic, epigenomic and transcriptomic analyses, as well as genome editing, compared to a non-matched generic reference.

Analysis of data from a large number of deep brain stimulation (DBS) recipients in North America has revealed a higher rate of revisions and removals of DBS leads than was previously reported. Hardware malfunction, lead infection and malpositioning were the most frequent reasons for revision or removal.

Inborn errors of the alternative NF-κB pathway in humans impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases

SARS-CoV-2 can infect cats and dogs, but the extent to which pets are infected in households remains unclear. Here, Patterson et al. test 919 companion animals in northern Italy and find that some dogs and cats from COVID-19 positive households can test positive for COVID-19 neutralizing antibodies, with dogs significantly more likely to do so if they came from COVID-19 positive households.

For the development and application of quantum technologies, devices capable of implementing more than two-photon processes are vital. Towards this aim, Spagnolo et al.build a three-port beam splitter and demonstrate mutual interference between the three photons.

Here Leonettiet al. report the observation of single-mode states in the regime of transverse Anderson localization in a disordered optical fibre, with negligible crosstalk accompanied by an inherent resilience to fibre bending and invariance with respect to the launch conditions.

Mammalian genomes are scattered with repetitive sequences, but their biology remains largely elusive. Here, the authors show that transcription can initiate from short tandem repetitive sequences, and that genetic variants linked to human diseases are preferentially found at repeats with high transcription initiation level.

Genome-wide association analyses identify 30 risk loci for IgA nephropathy. Functional annotations of putative causal genes converge on inflammatory signaling pathways and cytokine ligand–receptor pairs, prioritizing potential new drug targets.

Colloidal suspensions are known to exhibit interesting phase transitions. Here, the authors report a glass–glass transition with an associated waiting time in a colloidal clay (Laponite) under ambient conditions.

Stacking two-dimensional crystals creates a moiré superpotential that confines excitons. Here, temperature-/time- and magnetic field-dependent optical spectroscopy allows identifying the conditions under which excitons escape from the moiré potential

Protein corona formation is known to have significant effects upon nanomaterials application. Here, the authors investigate the creation of a protein coating on liposomes with the aim of improving liposome circulation time by avoiding leukocyte capture and demonstrated application in vitro and ex vivo.

Organic bioelectronic devices can be used to convert biological recognition events to a signal output. Here, the authors show how a water gated field-effect transistor modified with odorant binding proteins can be used to analyse the enantioselectivity of carvone binding and also estimate free-energy changes.

The human transferrin receptor 1 (CD71) is a transmembrane protein responsible for iron uptake. Here the authors present the 3.9 Å resolution cryo-EM structure of the CD71 ectodomain-human ferritin (H-Ft) complex and find that H-Ft binds a CD71 region different from the transferrin one that overlaps with the surface recognized by select pathogens.

Hidalgo and colleagues describe a cell-intrinsic program that induces changes in the proteome, granule content and NET-forming capacity of neutrophils and is driven by the chemokine receptor CXCR2 and regulators of the circadian clock.

The RNA binding protein FUS functions in several RNA biosynthetic processes and has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS). Here the authors show that FUS controls back-splicing reactions leading to circular RNA (circRNA) production in stem cell-derived motor neurons and that ALS-associated FUS mutations affect the biogenesis of circRNAs.

Using propensity score matching, Kim et al. find evidence of higher short- and long-term risk of adverse neuropsychiatric outcomes in Korean and Japanese cohorts of individuals infected with SARS-CoV-2 than in the general population.

Human primary and metastatic tumors harbor CD4⁺ T_reg cells that can suppress antitumor immune responses. Bonnal et al. identify an intratumoral type 1 T_reg-like CD4⁺ T cell subset that expresses the transcription factor EOMES, granzyme K and CHI3L2. This EOMES⁺ T cell subset correlates with disease progression but is responsive to PD-1 checkpoint blockade immunotherapy.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

Muscular Dystrophy can be caused by mutations in the dystrophingene, causing the severe Duchenne form or the mild Becker form depending on if the transcript is in or out-of-frame. Here the authors identify a Duchenne-type mutation that gives a Becker-like phenotype due to skipping of exon 45.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Chronic intestinal inflammatory diseases including ulcerative colitis and Crohn’s disease display extensive heterogeneity in the immunopathology, disease manifestation and response to treatment. Here the authors apply single cell transcriptomic and spatial molecular imaging, and characterise macrophage and neutrophils in samples from patients with inflammatory bowel diseases.

Though effective for parkinsonian motor symptoms, deep brain stimulation (DBS) of the subthalamic nucleus has variable effects on speech. A new study focusing on patients' perceptions reported that DBS recipients complain of greater speech disturbance than do non-DBS recipients. Patients should be made more aware of this possible adverse effect of DBS.

Here, the authors generated an artificial RNA molecule, or aptamer, specific for the Amyotrophic Lateral Sclerosis protein TDP-43. By interacting avidly with its target, the aptamer can be exploited to track TDP-43 phase transition in vitro and in cells.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.