State of play in amyotrophic lateral sclerosis genetics

Renton, Alan E.; Chiò, Adriano; Traynor, Bryan J.

doi:10.1038/nn.3584

Cited by 1,351 publications

(1,205 citation statements)

References 100 publications

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“…An escalating library of data in this regard is available through an online registry (http://alsod.iop.kcl.ac.uk) [87]. The hope is that a potential etiology, at least for a specific phenotype, will emerge and highlight a primary disease mechanism [3,5,88,89].…”

Section: The Role Of Molecular Biology In Understanding Als/mndmentioning

confidence: 99%

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Rosenfeld¹,

Strong

2015

Neurotherapeutics

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With the acceleration in our understanding of ALS and the related motor neuron disease has come even greater challenges in reconciling all of the proposed pathogenic mechanisms and how this will translate into impactful treatments. Fundamental issues such as diagnostic definition(s) of the disease spectrum, relevant biomarkers, the impact of multiple novel genetic mutations and the significant effect of symptomatic treatments on disease progression are all areas of active investigation. In this review, we will focus on these key issues and highlight the challenges that confront both clinicians and basic science researchers.

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Section: The Role Of Molecular Biology In Understanding Als/mndmentioning

confidence: 99%

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Rosenfeld¹,

Strong

2015

Neurotherapeutics

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“…No effective therapy is available for ALS, and understanding the disease pathogenesis could help in developing effective treatments. The majority of ALS cases are sporadic while familial forms account only for 10% of all ALS [2]. Twenty percent of inherited ALS is caused by mutations in the gene encoding for superoxide dismutase 1 (SOD1), an ubiquitously expressed enzyme functioning in the clearance of potentially toxic superoxide radicals.…”

Section: Introductionmentioning

confidence: 99%

SOD1 stimulates lamellipodial protrusions in Neuro 2A cell lines

Ferrari

Verpelli

Crespi

et al. 2018

Communicative & Integrative Biology

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We here investigated the effects of overexpressed superoxide dismutase (SOD)1 and amyotrophic lateral sclerosis (ALS)-linked SOD1 mutants G93A and G147S in Neuro 2A (N2A) cell lines, and found a three-fold increase in lamellipodia either in cells cultured under differentiated or undifferentiated growth conditions. In undifferentiated N2A cells, SOD1 constructs promoted lamellipodial protrusions to similar extent as the overexpression of Rac1, and SOD1-mediated lamellipodia were prevented by coexpression of the N17 dominant-negative form of Rac1, or shRNA for a downstream effector of Rac1, the insulin receptor tyrosine kinase substrate p53 (IRSp53) or its binding partner LIN7. Moreover, no additive effect was measured by coexpression of the SOD1 constructs with Rac1, IRSp53 or LIN7. Collectively these data support a role for SOD1 in the regulation of Rac1-mediated lamellipodia pathway, a property fully retained by the two SOD1 mutants.

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“…The worldwide incidence of ALS is 2-4 cases per 100,000 persons, although there is some ethnic variation [3]. The disease is sporadic in about 85 % of cases and is familial in about 15 % of cases [4]. The average survival is 3-5 years from symptom onset [1].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

2015

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Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor neurons without a known cure. Based on the possibility of cellular neuroprotection and early preclinical results, stem cells have gained widespread enthusiasm as a potential treatment strategy. Preclinical models demonstrate a protective role of engrafted stem cells and provided the basis for human trials carried out using various types of stem cells, as well as a range of cell delivery methods. To date, no trial has demonstrated a clear therapeutic benefit; however, results remain encouraging and are the basis for ongoing studies. In addition, stem cell technology continues to improve, and induced pluripotent stem cells may offer additional therapeutic options in the future. Improved disease models and clinical trials will be essential in order to validate stem cells as a beneficial therapy.

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State of play in amyotrophic lateral sclerosis genetics

Cited by 1,351 publications

References 100 publications

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

Challenges in the Understanding and Treatment of Amyotrophic Lateral Sclerosis/Motor Neuron Disease

SOD1 stimulates lamellipodial protrusions in Neuro 2A cell lines

Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis

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