A comprehensive review of amyotrophic lateral sclerosis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease affecting motor neurons with an incidence of about 1/100,000. Most ALS cases are sporadic, but 5–10% of the cases are familial ALS. Both sporadic and familial ALS (FALS) are associated with degeneration of cortical and spinal motor neurons. The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, genetic factors, symptoms, diagnostic, treatment, and even the available supplement and management of ALS. This will provide the reader with an advantage of receiving a broad range of information about the disease.

Related collections

Most cited references 585

Record: found
Abstract: found
Article: not found

RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.

Christopher J Donnelly, Ping-Wu Zhang, Jacqueline T Pham … (2013)

A hexanucleotide GGGGCC repeat expansion in the noncoding region of the C9ORF72 gene is the most common genetic abnormality in familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The function of the C9ORF72 protein is unknown, as is the mechanism by which the repeat expansion could cause disease. Induced pluripotent stem cell (iPSC)-differentiated neurons from C9ORF72 ALS patients revealed disease-specific (1) intranuclear GGGGCCexp RNA foci, (2) dysregulated gene expression, (3) sequestration of GGGGCCexp RNA binding protein ADARB2, and (4) susceptibility to excitotoxicity. These pathological and pathogenic characteristics were confirmed in ALS brain and were mitigated with antisense oligonucleotide (ASO) therapeutics to the C9ORF72 transcript or repeat expansion despite the presence of repeat-associated non-ATG translation (RAN) products. These data indicate a toxic RNA gain-of-function mechanism as a cause of C9ORF72 ALS and provide candidate antisense therapeutics and candidate human pharmacodynamic markers for therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

0 comments Cited 376 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration.

Zu-Hang Sheng, Qian Cai (2012)

Mitochondria have a number of essential roles in neuronal function. Their complex mobility patterns within neurons are characterized by frequent changes in direction. Mobile mitochondria can become stationary or pause in regions that have a high metabolic demand and can move again rapidly in response to physiological changes. Defects in mitochondrial transport are implicated in the pathogenesis of several major neurological disorders. Research into the mechanisms that regulate mitochondrial transport is thus an important emerging frontier.

0 comments Cited 337 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: found

Is Open Access

Amyotrophic lateral sclerosis

Lokesh C Wijesekera, P. Leigh (2009)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.

0 comments Cited 331 times – based on 0 reviews      Review now

All references

Author and article information

Contributors

Sara Zarei

Karen Carr

Luz Reiley

Kelvin Diaz

Orleiquis Guerra

Pablo Fernandez Altamirano

Wilfredo Pagani

Daud Lodin

Gloria Orozco

Angel Chinea

Journal

Journal ID (nlm-ta): Surg Neurol Int

Journal ID (iso-abbrev): Surg Neurol Int

Journal ID (publisher-id): SNI

Title: Surgical Neurology International

Publisher: Medknow Publications & Media Pvt Ltd (India )

ISSN (Print): 2229-5097

ISSN (Electronic): 2152-7806

Publication date Collection: 2015

Publication date (Electronic): 16 November 2015

Volume: 6

Electronic Location Identifier: 171

Affiliations

[1]Department of Medicine, San Juan Bautista School of Medicine, Caguas, USA

[1 ]Neurologist, Caribbean Neurological Center, Caguas, USA

Author notes

[* ]Corresponding author

Article

Publisher ID: SNI-6-171

DOI: 10.4103/2152-7806.169561

PMC ID: 4653353

PubMed ID: 26629397

SO-VID: 659921d7-064a-449c-8c3f-b09114e81849

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

A comprehensive review of amyotrophic lateral sclerosis

Read this article at

Abstract

Related collections

International Journal of Applied Technology in Medical Sciences

Most cited references 585

RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.

Mitochondrial transport in neurons: impact on synaptic homeostasis and neurodegeneration.

Amyotrophic lateral sclerosis

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 482

Cited by 251

Most referenced authors 3,772