Amyotrophic lateral sclerosis

  title={Amyotrophic lateral sclerosis},
  author={Michael A. van Es and Orla Hardiman and Adriano Chi{\`o} and Ammar Al-Chalabi and R. Jeroen Pasterkamp and Jan Herman Veldink and Leonard H. Berg},
  journal={The Lancet},

Figures and Tables from this paper

Genetics of amyotrophic lateral sclerosis: A review

Novel therapeutic targets for amyotrophic lateral sclerosis

An overview of the contribution of different targets like mitochondrial dysfunction, glutamate transport and excitotoxicity, protein accumulation, Oxidative stress, neuromuscular junction, microglia, and other molecular targets in the pathogenesis of ALS are provided.

Family history of neurodegenerative disorders in patients with amyotrophic lateral sclerosis: population-based case–control study

This prospective case–control study aimed to describe the family aggregation of ND within the group of patients with ALS and to estimate the risk of ALS development in patients with a positive ND family history.

Psychiatric Symptoms in Amyotrophic Lateral Sclerosis: Beyond a Motor Neuron Disorder

This review aims at identifying the most common psychiatric alterations related to ALS and its prognosis, looking at a common genetic background and shared structural brain pathology.

Sensory nerve disturbance in amyotrophic lateral sclerosis

Astrocytes in Motor Neuron Diseases.

A dissertation is substantiated by the findings that built awareness on the glial involvement and how the glia-neuronal interplay is perturbed, along with the appraisal of this new cellular site for possible therapeutic intervention.

Cortical Circuit Dysfunction as a Potential Driver of Amyotrophic Lateral Sclerosis

The possibility that initial cortical circuit dysfunction might act as the main driver of ALS onset and progression is discussed and the potential cellular and molecular origins of cortical hyperexcitability in ALS is evaluated.

Inherited and Sporadic Amyotrophic Lateral Sclerosis and Fronto-Temporal Lobar Degenerations arising from Pathological Condensates of Phase Separating Proteins.

This review uses the FUS, TDP-43 and A11 proteins as examples to illustrate how missense mutations and aberrant post-translational modifications of these proteins cause amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration (FTLD).



State of play in amyotrophic lateral sclerosis genetics

Current literature of the major genes underlying ALS, SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, C9ORF72 and PFN1 are summarized and how each new genetic discovery is broadening the phenotype associated with the clinical entity the authors know as ALS is outlined.

A mutation in sigma‐1 receptor causes juvenile amyotrophic lateral sclerosis

A consanguineous family segregating juvenile ALS in an autosomal recessive pattern is described and the genetic variant responsible for the disorder is described.

ANG mutations segregate with familial and 'sporadic' amyotrophic lateral sclerosis

The finding of seven missense mutations in 15 individuals, of whom four had familial ALS and 11 apparently 'sporadic' ALS, provides further evidence that variations in hypoxia-inducible genes have an important role in motor neuron degeneration.

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis

Findings further corroborate that TDP-43 is involved in ALS pathogenesis and reports eight missense mutations in nine individuals—six from individuals with sporadic ALS and three from those with familial ALS (FALS)—and a concurring increase of a smaller T DP-43 product.

Gene discovery in amyotrophic lateral sclerosis: implications for clinical management

It is observed that many gene variants associated with ALS have effect sizes between those of mutations that greatly increase risk and those of common variants that have a small effect on risk, and this observation is combined with insights from next-generation sequencing to explore the implications for genetic counselling.

Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis

Ongoing research on the cellular pathways highlighted in this Review is predicted to open the door to new therapeutic interventions to slow disease progression in ALS.

Mutations of optineurin in amyotrophic lateral sclerosis

It is shown that there are mutations in the gene encoding optineurin (OPTN), earlier reported to be a causative gene of primary open-angle glaucoma (POAG), in patients with ALS and these findings strongly suggest that OPTN is involved in the pathogenesis of ALS.

Amyotrophic lateral sclerosis.

Tremendous progress has been made in the field of ALS based on recent neuropathological and genetic discoveries and the role of metabolism and nutrition in the pathogenesis of the disease is debated and may potentially serve as a future therapeutic target.

Projected increase in amyotrophic lateral sclerosis from 2015 to 2040

The number of ALS cases across the globe will increase from 222,801 in 2015 to 376,674 in 2040, representing an increase of 69%.