Amyotrophic lateral sclerosis (ALS), cancer, autoimmunity and metabolic disorders: An unsolved tantalizing challenge

Riancho, Javier; Delgado-Alvarado, Manuel; Andreu, Maria Dolores; Paz-Fajardo, Lucía; Arozamena, Sara; Gil-Bea, Francisco J.; Munáin, Adolfo López de

doi:10.1111/bph.15151

Cited by 11 publications

(10 citation statements)

References 85 publications

(201 reference statements)

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“…These authors described ALS as a complex disease caused by individual genetic risk, ageing and the influence of environmental factors, which interact to determine the threshold for the onset, progression and prognosis of the disease. They discuss the relevance, for the disease, of those environmental conditions that could be modified and review the evidence for cancer, autoimmunity and metabolic disorders, as important conditions leading to ALS (Riancho et al, 2020).…”

Section: Figurementioning

confidence: 99%

Recent advances in the pathogenesis and therapeutics of amyotrophic lateral sclerosis

Fernández‐Ruiz

Lago

Rodríguez‐Cueto

et al. 2021

British J Pharmacology

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Recent advances in the pathogenesis and therapeutics of amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) is a progressive and highly disabling neurodegenerative disorder, with an incidence of 1-5 cases/100,000 subjects and characterized by muscle denervation, weakness, atrophy, and paralysis, frequently leading to patient death (by respiratory failure) in 3-5 years after diagnosis. The disease starts with a progressive loss of upper and lower motor neurons triggered by a complex aetiology (genes and environmental factors). Sporadic forms of the disease are the most abundant (up to 90% of cases), but they are clinically and histopathologically indistinguishable from the different familial forms described so far, which involve mutations in more than 25 ALS-related genes, among which the most relevant, for different reasons, are (i) SOD1 encoding the key antioxidant enzyme superoxide dismutase-1; (ii) TARDBP and FUS encoding the proteins TAR-DNA binding protein-43 (TDP-43) or fused in sarcoma (FUS), respectively, involved in pre-mRNA splicing, transport, and stability; and (iii) C9orf72 encoding a protein involved in intracellular trafficking in neurons and other cell functions not completely understood yet. Changes in SOD-1, TARDBP, FUS, and C9orf72 are present in most of the cases (approximately 70%) of familial ALS (Kim, Gautier, Tassoni-Tsuchida, Ma, & Gitler, 2020). SOD1 was the first ALS-related gene to be identified in 1993 (Rosen et al., 1993), and its discovery represented an important drive in the research in ALS, in part derived from the rapid development of transgenic animal models (most of them in mice) overexpressing the different human SOD1 mutations (the most abundant being G93A;

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Section: Figurementioning

confidence: 99%

Recent advances in the pathogenesis and therapeutics of amyotrophic lateral sclerosis

Fernández‐Ruiz

Lago

Rodríguez‐Cueto

et al. 2021

British J Pharmacology

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“…The ALS pathway, which is a progressive and lethal motor disorder, includes in its gene list TP53, several members of the caspase family pathway, TNF and MAP kinases; all of these genes are widely documented as important agents in many cancer phenotypes [ 91 – 94 ]. Furthermore, a 2016 preclinical study showed how the C9orf72 knockout, the most common cause of ALS, caused an unexpected increase in tumours in mice [ 95 ].…”

Section: Discussionmentioning

confidence: 99%

The regulatory landscape of retinoblastoma: a pathway analysis perspective

et al. 2022

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Retinoblastoma (Rb) is a rare intraocular tumour in early childhood, with an approximate incidence of 1 in 18 000 live births. Experimental studies for Rb are complex due to the challenges associated with obtaining a normal retina to contrast with diseased tissue. In this work, we reanalyse a dataset that contains normal retina samples. We identified the individual genes whose expression is different in Rb in contrast with normal tissue, determined the pathways whose global expression pattern is more distant from the global expression observed in normal tissue, and finally, we identified which transcription factors regulate the highest number of differentially expressed genes (DEGs) and proposed as transcriptional master regulators (TMRs). The enrichment of DEGs in the phototransduction and retrograde endocannabinoid signalling pathways could be associated with abnormal behaviour of the processes leading to cellular differentiation and cellular proliferation. On the other hand, the TMRs nuclear receptor subfamily 5 group A member 2 and hepatocyte nuclear factor 4 gamma are involved in hepatocyte differentiation. Therefore, the enrichment of aberrant expression in these transcription factors could suggest an abnormal retina development that could be involved in Rb origin and progression.

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“…One limitation of the study was that ALS death rather than incidence was used in CPS-II Nutrition (the Cancer Prevention Study II-Nutrition Cohort), MEC (the Multiethnic Cohort Study), and NIH-AARP (the National Institutes of Health-Association of American Retired Persons Diet and Health Study). However, due to the rapidly progressive nature of ALS (median survival 1 4 1.5-3 years), the authors assumed ALS death to be a reasonable proxy for incidence.…”

Section: Urates and Purinesmentioning

confidence: 99%

“…Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem [1]. As a rule, patients die from respiratory failure 3-5 years after onset of the disease.…”

Section: Introductionmentioning

confidence: 99%

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis

Goncharova

Davydova²,

Попова³

et al. 2021

Nutrients

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Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. Methods: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010–2020. Discussion: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. Conclusion: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study.

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Amyotrophic lateral sclerosis (ALS), cancer, autoimmunity and metabolic disorders: An unsolved tantalizing challenge

Cited by 11 publications

References 85 publications

Recent advances in the pathogenesis and therapeutics of amyotrophic lateral sclerosis

Recent advances in the pathogenesis and therapeutics of amyotrophic lateral sclerosis

The regulatory landscape of retinoblastoma: a pathway analysis perspective

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis

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