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This Perspective centres on alterations in the fatty acid-ome as the critical feature of lipid aberration in α-synucleinopathies, specifically Parkinson disease. Here, the authors explain the biological and genetic basis for their hypothesis, with an emphasis on the transient binding of α-synuclein to fatty acids of various lipids.
Many autoimmune and genetic causes of sporadic late-onset cerebellar ataxia (SLOCA) can now be identified, but some individuals remain categorized as having idiopathic SLOCA. Wirth and colleagues discuss advanced genomic techniques that might identify additional ‘missing’ SLOCA causes, potential prognostic biomarkers and progress towards effective treatments.
Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adulthood and among the most clinically diverse monogenic diseases. This Review summarizes the latest insights into the molecular underpinnings of DM1, highlighting the implications for therapy development.
Non-invasive brain stimulation (NIBS) shows considerable promise as a therapeutic strategy for neurological and psychiatric disorders. This Review explores the role of NIBS techniques, including repetitive transcranial magnetic stimulation and transcranial electrical stimulation, for treating cognitive impairments, speech and language difficulties, and motor control deficits in people with neurodegenerative or brain lesion disorders.
This Review considers the aetiology of health disparities in neurology at an individual, interpersonal, community and societal level, and suggests practical interventions to address the multifactorial issues.
Management of autoimmune neuropathies has remained unchanged for much of the past 30 years, but recent advances are changing the rate of progress. In this Review, the authors summarize the latest developments, including discoveries in disease mechanisms, new diagnostic guidelines, identification of new biomarkers and the status of promising clinical trials.
The neuronal ceroid lipofuscinoses, or Batten disease, are a group of fatal inherited neurodegenerative lysosomal storage disorders. Despite having defined genetic causes, the underlying disease mechanisms remain poorly understood and treatments are limited. Cooper and colleagues highlight recent advances in understanding the cell biology and disease pathogenesis, which could inform future therapeutic development.
Deep brain stimulation (DBS) is a highly effective treatment option for movement disorders and is also being explored for other brain disorders. This Perspective proposes a unified framework, termed adaptive circuit targeting, which combines adaptive and connectomic DBS to enable decoding of symptom severity from brain signals and activation of relevant symptom-response circuits.
Earlier this year, the Nav1.8 channel inhibitor suzetrigine became the first new pain therapeutic to be approved in 20 years. Here, Waxman et al. discuss the challenges of improving Nav1.8-targeted relief for acute pain and the translation to chronic pain.
Spreading depolarization is widely accepted as the cause of migraine aura, but its relationship with migraine headache is less clear. In this Review, Harriott and Ayata review the evidence that links spreading depolarization with the headache phase of migraine with aura, and consider the potential of therapeutic targeting of spreading depolarization in migraine.
Neurodegenerative diseases such as Alzheimer disease, Parkinson disease, frontotemporal lobar degeneration and multiple system atrophy are characterized pathologically by deposition of specific proteins in the brain. This article reviews the latest advances in the development of PET radiotracers for neurodegenerative proteinopathies and highlights the diagnostic and therapeutic applications of this technology.
Low-income and middle-income countries bear a high burden from dementia that is not reflected in research. This Review outlines the reasons for this disparity and explores the challenges and opportunities of dementia research in low-income and middle-income countries.
The modulating influence of biological sex on clinical variability, disease trajectories and treatment response represents a nascent topic in frontotemporal dementia (FTD) research. Recent empirical studies leveraging large-scale consortium data illuminate how biological sex impinges on — and potentially interacts with — variations in clinical symptomatology, pathophysiology and disease trajectory in FTD.
Approximately half of the people currently with multiple sclerosis (MS) are ≥50 years of age, yet guidelines for management of MS in older age are lacking. This Consensus statement presents the outcomes of an International Advisory Committee on Clinical Trials (IACCT) in MS workshop on ageing and MS, including recommendations for advancing research, care and awareness.
Here, Rafii and Aisen review recent progress surrounding the approvals of amyloid-targeting monoclonal antibodies, the first disease-modifying therapies for Alzheimer disease. The Review highlights key factors that affect the integration of these treatments into clinical practice and explores future directions.
In this Review, the authors describe perturbations in neuroimmune, metabolic and oxidative pathways in major depressive disorder and explore how imbalances in each of these pathways can contribute to the acute phase of the disease.
This Perspective article explores the efficacy of multimodal lifestyle interventions to tackle the rising incidence of dementia in low- and middle-income countries. The authors discuss a contextual adaptation of the Finnish FINGER trial, Africa-FINGERS, which is pioneering a culturally relevant, multidomain approach to dementia risk reduction for African settings.
Chimeric antigen receptor (CAR) T cells provide an effective treatment option for advanced haematological malignancies, but neurological adverse effects of CAR T cell therapies are common. This article reviews current knowledge regarding the mechanisms that contribute to neurological toxicities following CAR T cell therapy and highlights current and emerging management strategies.
This Review considers how DNA methylation-based biomarkers can be used to monitor brain ageing and stratify neurological disease risk. The authors focus on epigenetic clocks, which can be applied across multiple tissues to estimate biological ageing, and blood-based epigenetic scores, which can track brain-based phenotypes and risk factors for neurological disease.
