Review Articles

Bruton tyrosine kinase inhibitors are an emerging treatment for multiple sclerosis. Krämer et al. consider the evidence that central nervous system-penetrant Bruton tyrosine kinase inhibitors might target both peripheral immune cells and compartmentalized inflammation and discuss promising preliminary results of clinical trials of these agents in multiple sclerosis.

In the field of Alzheimer disease genetics, a lack of ancestral diversity in study cohorts is limiting progress. Here, the authors summarize our current knowledge of Alzheimer disease genetics in populations across the world and highlight efforts to increase cohort diversity.

This Review highlights how two discoveries — expression of α7 nicotinic acetylcholine receptors (α7nAChRs) by astrocytes and a correlation between astrocytic α7nAChR overexpression and amyloid-β pathology — are bridging the gap between the cholinergic and amyloid cascade hypotheses of Alzheimer disease pathogenesis.

In this Review, the authors discuss recent efforts to predict disease onset, treatment response and disease outcome in individuals with psychosis. They cover genetic, biological, clinical and environmental predictive factors and assess whether the variation in outcomes is attributable to differences in the pathophysiology of psychosis.

Chronic neuropathic pain is a leading cause of disability that remains therapeutically challenging. Here, Fiore et al. review the immune mechanisms that contribute to the resolution of chronic neuropathic pain. Contributions of the gut microbiome and specialized pro-resolving mediators are also discussed, along with potential therapeutic strategies.

Wilson et al. review our current knowledge of the extracellular proteostasis system that protects the brain from the pathological consequences of extracellular protein aggregation. They discuss growing evidence that impairment of this system contributes to neuronal death in neurodegenerative diseases.

This article reviews key pathogenic mechanisms underlying the development of CNS autoimmunity, focusing on the role of autoantibodies that target neuronal and/or glial cell-surface antigens. The authors consider novel therapeutic approaches based on knowledge of the immunopathogenesis of autoimmune CNS disorders.

In this Review, the authors provide an overview of the evidence indicating that multiple sclerosis is a rare complication of infection with the Epstein–Barr virus and discuss the mechanisms that could underlie this association.

Here, Sven Bölte and colleagues consider the effects of sex and gender on neurodevelopmental conditions. They discuss the available epidemiological, behavioural, neurobiological and endocrinological evidence and highlight the importance of further research in this area.

Here, Timothy Steiner and Lars Stovner discuss the progression of migraine epidemiology over the last seven decades and question the apparent increase in migraine prevalence over time.

Facioscapulohumeral muscular dystrophy is caused by aberrant expression of the transcription factor DUX4. Tihaya, Mul and colleagues describe advances in the development of targeted treatments for facioscapulohumeral muscular dystrophy and discuss potential clinical trial outcome measures as well as molecular and imaging biomarkers.

Advances in neuroimaging research have enabled the development of predictive models that integrate information from multiple brain systems. Here, Perovnik, Rus and colleagues discuss the detection and validation of neurodegenerative disease-specific functional brain networks and consider their relationship to pathological processes and disease-related genotypes.

Here, Spires-Jones and colleagues review our current understanding of the mechanisms underlying synaptic degeneration in Alzheimer disease and highlight key questions that still need to be answered. They also discuss novel therapeutic approaches that target the synapse.

Amyotrophic lateral sclerosis (ALS) is a devastating, incurable disease characterized by progressive loss of upper and lower motor neurons. Here, the authors describe the current landscape of genetic therapies for ALS and discuss new opportunities for gene replacement therapy, focusing on loss-of-function mutations.

In this Review, Savitz and Cox consider the evidence for a model of cell-based therapy referred to as the bioreactor hypothesis, in which exogenous cells migrate to peripheral organs and reprogramme host immune cells to generate an anti-inflammatory, regenerative environment.

In this Review, the authors provide an overview of evidence that activity-regulated myelination is required for brain adaptation and learning, and discuss how dysregulation of activity-dependent myelination contributes to neurological disease and could be a new therapeutic target.

Here, the authors discuss the potential effects of social determinants of health on multiple sclerosis risk and outcomes. They suggest that addressing these determinants of health could substantially improve the lives of individuals with multiple sclerosis and call for more research.

In this Review, Vezzani et al. discuss how dysregulation of key astrocyte functions — gliotransmission, cell metabolism and immune function — contribute to the development and progression of hyperexcitability in epilepsy and consider strategies to mitigate astrocyte dysfunction.

In this Review, Eichmüller and Knoblich discuss how human brain organoids can recapitulate the unique processes that occur in human brain development and how they can complement classical approaches to revolutionize research into neurological diseases.

Most cases of Alzheimer disease (AD) have a complex aetiology, probably involving multiple genetic and environmental factors. In this Review, the authors discuss how various environmental AD risk factors could induce epigenetic modifications of key AD-associated genes and pathways.