The changing scene of amyotrophic lateral sclerosis

  title={The changing scene of amyotrophic lateral sclerosis},
  author={Wim Robberecht and Thomas Ernest James Philips},
  journal={Nature Reviews Neuroscience},
Several recent breakthroughs have provided notable insights into the pathogenesis of amyotrophic lateral sclerosis (ALS), with some even shifting our thinking about this neurodegenerative disease and raising the question as to whether this disorder is a proteinopathy, a ribonucleopathy or both. In addition, these breakthroughs have revealed mechanistic links between ALS and frontotemporal dementia, as well as between ALS and other neurodegenerative diseases, such as the cerebellar atrophies… 

The genetic basis of amyotrophic lateral sclerosis: recent breakthroughs

The genetic basis of ALS is discussed, and the causal genes to three highly interrelated pathogenic mechanisms: dysproteostasis, RNA dysregulation, and axon dysfunction are linked.

Genetics of Amyotrophic Lateral Sclerosis.

Findings from ALS genetics provide new insight into therapies that target genetically distinct subsets of ALS and FTD, as well as numerous downstream pathophysiological events.

The phenotypic variability of amyotrophic lateral sclerosis

The phenotypic variability of ALS is reviewed and how it is reflected in familial and sporadic ALS, in the degree of upper and lower motor neuron involvement, in motor and extramotor involvement, and in the spectrum of ALS and frontotemporal dementia.

Barriers to novel therapeutics in amyotrophic lateral sclerosis

The prevalent barriers, including clinical and genetic variability of amyotrophic lateral sclerosis, frailty of the current mouse model and inadequateness of clinical trials, are discussed in the search for novel therapeutics.

Amyotrophic Lateral Sclerosis: Current Therapeutic Perspectives

This chapter focuses on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discusses their impact on disease progression, and summarizes the progress in the non-pharmacological therapy trials in ALS.

Diagnostic Challenge and Neuromuscular Junction Contribution to ALS Pathogenesis

A combination of further research on the NMJ parameters that are specific for this disease and laboratory tests are crucial for the early determination of specific changes in the muscle, as well as in motor neuron and the prediction of ALS progression.

Key Molecular Mechanisms in the Pathogenesis of Amyotrophic Lateral Sclerosis (ALS)

This review focuses on the recent findings to elucidate potential molecular mechanisms for ALS and suggests that endoplasmic reticulum stress and the UPR pathway, autophagy and apoptosis may be implicated in the pathogenesis of ALS.

The Emerging Roles of MicroRNAs in the Pathogenesis of Frontotemporal Dementia–Amyotrophic Lateral Sclerosis (FTD-ALS) Spectrum Disorders

The authors will focus on microRNAs and review the emerging roles of these small RNAs in several aspects of FTD-ALS pathogenesis, setting the stage for further understanding of the disorder.



Pathological TDP‐43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations

This study investigated TDP‐43 in a larger series of ALS cases, including familial cases with and without SOD1 mutations, and identified it as the major pathological protein in sporadic ALS.

The overlap of amyotrophic lateral sclerosis and frontotemporal dementia

Patients with frontotemporal dementia with no known diagnosis of ALS or family history of ALS were clinically and electrophysiologically assessed for the presence of ALS and two had EMG findings suggestive of denervation in one limb.

Differential involvement of optineurin in amyotrophic lateral sclerosis with or without SOD1 mutations.

Evidence is provided that optineurin is involved in the pathogenesis of sporadic ALS and non- SOD1 familial ALS, thus supporting the hypothesis that these forms of ALS share a pathway that is distinct from that of S OD1-linked 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.

Nogo Provides a Molecular Marker for Diagnosis of Amyotrophic Lateral Sclerosis

The alteration in Nogo expression pattern, common to sporadic and familial ALS, represents a potential diagnosis tool and points strongly to Nogo having a central role in disease.

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.