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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that is marked by fasciculation, spasticity and progressive weakness of muscles, and results in difficulty speaking, swallowing and breathing. ALS is fatal, usually leading to death within a few years from diagnosis, although more slowly progressing forms of the disease exist.
In this Perspective, the authors propose a new classification system for amyotrophic lateral sclerosis and related neurodegenerative disorders that recognizes, in parallel, the clinical syndromes and the underlying biology of disease. The framework emerged from discussions at the Second International Pre-Symptomatic ALS Workshop in Miami (February 2023).
Multilingual articulatory representations in the speech-motor cortex of a participant with vocal-tract and limb paralysis enabled the development of a bilingual speech neuroprosthesis.
Amyotrophic Lateral Sclerosis is characterized by TDP-43 proteinopathy in the brain. Here, the authors find TDP-43 aggregation might be mediated by the loss of Asparaginase-like 1, an enzyme that degrades detrimental isoaspartates and is downregulated by the endogenous retrovirus HML-2.
Amyotrophic Lateral Sclerosis (ALS) is highly heritable but the mechanisms of sporadic ALS are not fully understood. In this study, the authors identify drivers of variation and disease-relevant changes in the epigenomic profile of iPSC-derived motor neuron lines generated from ALS patients and healthy controls as part of the Answer ALS program.
Expanded intronic G4C2 repeats in C9orf72 cause ALS/FTD. GR dipeptide repeats produced in C9orf72 ALS/FTD co-aggregate with Kap2 in neurons, affecting survival. Upregulating Kapβ2 may mitigate neurotoxicity, a potential therapy for C9orf72-ALS/FTD.
Around 10% of individuals with frontotemporal lobar dementia have amyloid filament inclusions that lack tau and TDP-43 and were thought to contain the protein FUS, but are found instead to contain the FUS homologue TAF15.
Two new studies have provided important mechanistic insights into TDP-43 pathology, a hallmark of neurodegenerative conditions such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration.