Review Articles

This Review explores several key dysregulated pathways in ALS (RNA processing, proteostasis, metabolism and inflammation) as well as evolving efforts to develop effective therapeutics to restore cellular homeostasis. The authors also detail strategies that are likely to be required to improve clinical studies moving forwards.

The immune system plays a major part in neurodegenerative diseases. In this Review, Weiner considers the contributions of several components of the immune system in multiple neurodegenerative diseases and their potential as shared therapeutic targets across these diseases.

Diabetic peripheral neuropathy (DPN) is length-dependent peripheral nerve damage that frequently arises as a complication of type 1 or type 2 diabetes, and even prediabetes. This Review highlights the global and regional burden of DPN and explores risk factors, including metabolic factors beyond hyperglycaemia, that could guide treatment and prevention strategies.

In this Review, the authors provide a comprehensive overview of our current understanding of the involvement of α-synuclein in neurodegenerative diseases and highlight therapeutic approaches that target pathological α-synuclein.

This Review summarizes the evidence for the role of diet in cognitive health, and it explores the limitations of diet intervention trials, which have yet to robustly support observational findings. The authors discuss potential underlying mechanisms and offer strategies for future trials to enhance the understanding of the role of diet in dementia prevention.

Effective treatments for the acute stages of intracerebral haemorrhage are currently limited. In this Review, the authors consider advances in therapeutic strategies and neurosurgical procedures, including acute care bundles, that promise a new era of interventions.

Parkinson disease (PD) poses substantial management challenges owing to progressive disability and emergence of levodopa-resistant symptoms and treatment-related complications. This Review examines the current state of research into symptomatic and disease-modifying PD therapies and outlines future priorities for advancing our understanding and treatment of the disease.

Peripheral organ dysfunction can have considerable effects on brain health, contributing to neurodegeneration and dementia. This Review explores how clinical and subclinical dysfunction of specific organ systems can impact brain health and discusses the implications for dementia prevention.

Traumatic brain injury can result in long-lasting symptoms and is associated with progressive neurodegenerative and neuroinflammatory pathology, but biomarkers to diagnose and monitor these chronic effects are lacking. Here, Thelin and co-workers summarize the available evidence for fluid biomarker use in chronic traumatic brain injury.

This Review summarizes the history and current concepts of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), including epidemiology, clinical and neuroimaging features and pathophysiology. It also discusses new molecularly targeted therapies for NMOSD that might be also applied to MOGAD in the future.

Pituitary adenylate cyclase-activating polypeptide signalling has been linked to migraine pathogenesis. In this Review, Ashina and co-workers explore the molecular and cellular mechanisms of pituitary adenylate cyclase-activating polypeptide signalling and discuss emerging therapeutic strategies to target this pathway for migraine treatment.

The approval of therapies for progressive multiple sclerosis has heightened the need for thorough assessment of disease progression and treatment response. This Review provides a comprehensive summary of available and emerging techniques, including advanced imaging, fluid biomarkers and patient-reported outcomes, highlighting their combined use for the accurate assessment of disease.

Stiff-person syndrome is an autoimmune neuronal hyperexcitability disorder that causes limb stiffness, painful spasms and falls, and increased awareness of the disease is creating diagnostic and management challenges. In this Review, Dalakas provides an overview of the current clinical and mechanistic understanding of stiff-person syndrome and related disorders and discusses current and emerging therapeutic interventions.

OnabotulinumtoxinA was first linked to beneficial effects in migraine 25 years ago and has since become a widely used treatment for chronic migraine. In this Review, Pozo-Rosich and colleagues consider the impact that onabotulinumtoxinA has had on the management of chronic migraine and on the research field.

Some patients who are treated with checkpoint inhibitors experience peripheral nervous system (PNS) immune-related adverse events (irAEs). O’Hare and Guidon describe the spectrum of PNS irAE phenotypes, discuss their underlying mechanisms and outline a consensus-based, pathophysiology-driven approach to their clinical management.

Vaccination has transformed the global fight against infectious diseases and has a highly favourable benefit–risk profile in most people, although adverse events, including neurological complications, can occasionally occur. This article reviews the links between vaccination and neurological disease and considers the role of neurologists in identifying safety signals and managing risk.

The association between the rare, monogenic lysosomal storage disorder Gaucher disease and Parkinson disease has provided insights into the pathogenesis of this far more common neurodegenerative disease. Here, Sidransky and colleagues review the knowledge gained from decades of Gaucher disease research and explore the relationship between GBA1 and parkinsonism.

Amyotrophic lateral sclerosis (ALS) differs considerably in prevalence and manifestation between sexes. This Review summarizes sexual dimorphism in the epidemiology, clinical presentation and disease mechanisms of ALS and explores the role of brain–body interactions in driving sex-dependent pathogenesis.

Apolipoprotein E (APOE) is the greatest genetic modulator of sporadic Alzheimer disease risk. This Review provides a comprehensive update on our current knowledge of the genetics of APOE and its role in Alzheimer and other neurodegenerative diseases, and summarizes emerging APOE-targeted therapies designed to prevent or slow down Alzheimer disease.

Overall survival rates for traumatic brain injury have improved, but affected individuals often experience persistent and debilitating long-term complications. In this Review, the authors discuss recent evidence for the role of spreading depolarization in the initiation of long-term pathology in traumatic brain injury, including effects on blood–brain barrier dysfunction and neuroinflammation.