Review Articles in 2022

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.

In this Review, the authors summarize the interactions of the neurovascular unit with systemic biology after ischaemic stroke, consider how these interactions influence stroke outcome, and discuss how these interactions could be targeted to improve outcomes.

In this Review, Fong and Inouye explore mechanisms that might be common to both delirium and dementia. They present delirium as a possible modifiable risk factor for dementia and discuss the importance of delirium prevention strategies in reducing this risk.

In this Review, the authors provide detailed insight into how the gut microbiota influences the immune system, with implications for neuroinflammation, and discuss the accumulating evidence that the gut microbiota is an important factor in multiple sclerosis pathogenesis and a potential therapeutic target.

This Review considers how variants in genes encoding proteins that regulate epigenetic mechanisms might contribute to epilepsy. The discussion is structured around five categories of epigenetic mechanisms: DNA methylation, histone modifications, histone–DNA crosstalk, non-coding RNAs and chromatin remodelling.

The prominence of gastrointestinal dysfunction among the non-motor features of Parkinson disease (PD) indicates a close bidirectional link between the brain and the gut. This Review discusses the proposed roles of gut-related factors in PD development, progression and treatment responses, and as therapeutic targets.

The fifth edition of the WHO classification of CNS tumours was published in 2021. Here, Horbinski and colleagues summarize the main changes in this new edition and discuss how each change will affect post-surgical treatment, clinical trial enrolment and cooperative studies.

In this Review, Oh and Bar-Or provide an overview of selected emerging therapies for multiple sclerosis with the potential to limit non-relapsing, progressive disease injury and to promote tissue repair, thereby addressing crucial unmet therapeutic needs.

Recent technological advances have enabled the detection of specific forms of phosphorylated tau in blood. Here, the authors summarize the performance of blood phosphorylated tau biomarkers in the context of Alzheimer disease and highlight related ethical, analytical and clinical challenges.

In this Review, Diener et al. discuss the concept of embolic stroke of undetermined source, proposing updates to the criteria and diagnostic algorithm in light of evidence gathered since the concept was first introduced.

The term ‘rapidly progressive dementia’ (RPD) describes a cognitive disorder with fast progression, leading to dementia within a relatively short time. This Review discusses the wide range of RPD aetiologies, as well as the diagnostic approach and treatment options.

In this Review, Coyne and Rothstein discuss disruptions to the nuclear pore complex and nucleocytoplasmic transport, which are emerging as pathological mechanisms in multiple neurodegenerative diseases, and consider the effects of these changes on cellular function and their potential for therapeutic targeting.