Omega-3 Hastens and Omega-6 Delays the Progression of Neuropathology in a Murine Model of Familial ALS

Boumil, Edward F.; Vohnoutka, Rishel; Yu-guan, Liu; Lee, Sang-Mook; Shea, Thomas B.

doi:10.2174/1874205x01711010084

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…For example, omega-3 supplementation in mouse models of ALS reported an increased cellular damage that could increase disease progression [ 120 ]. Similar results were obtained in a more recent study in a murine model of familial ALS [ 121 ]. However, combination of omega-3 and vitamin E could reduce ALS risks [ 33 ].…”

Section: Discussionsupporting

confidence: 91%

Amyotrophic Lateral Sclerosis: A Diet Review

D’Antona

Caramenti

Porro

et al. 2021

Foods

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Amyotrophic lateral sclerosis (ALS) is a fatal disease related to upper and lower motor neurons degeneration. Although the environmental and genetic causes of this disease are still unclear, some factors involved in ALS onset such as oxidative stress may be influenced by diet. A higher risk of ALS has been correlated with a high fat and glutamate intake and β-methylamino-L-alanine. On the contrary, a diet based on antioxidant and anti-inflammatory compounds, such as curcumin, creatine, coenzyme Q10, vitamin E, vitamin A, vitamin C, and phytochemicals could reduce the risk of ALS. However, data are controversial as there is a discrepancy among different studies due to a limited number of samples and the many variables that are involved. In addition, an improper diet could lead to an altered microbiota and consequently to an altered metabolism that could predispose to the ALS onset. In this review we summarized some research that involve aspects related to ALS such as the epidemiology, the diet, the eating behaviour, the microbiota, and the metabolic diseases. Further research is needed to better comprehend the role of diet and the metabolic diseases in the mechanisms leading to ALS onset and progression.

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Section: Discussionsupporting

confidence: 91%

Amyotrophic Lateral Sclerosis: A Diet Review

D’Antona

Caramenti

Porro

et al. 2021

Foods

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“…Going against the common perception that Ω-3 fatty acids are "healthy" and Ω-6s are "unhealthy," we counterintuitively found that Ω-3 levels were elevated, and Ω-6 levels diminished, in individuals at high genetic risk for ALS. Supporting this association, Ω-6s delayed disease progression in a mouse model of ALS, while Ω-3 supplementation hastened progression (34), suggesting dietary modulation of Ω-3 and Ω-6 fatty acids may be a useful therapeutic strategy for ALS. [Conversely, an observational epidemiological study found an inverse correlation between Ω-3 intake and ALS risk, and a nonsignificant correlation with Ω-6 intake ( 57). ]…”

Section: Noncanonical Disease-analyte Associationsmentioning

confidence: 93%

Multiomic blood correlates of genetic risk identify presymptomatic disease alterations

Wainberg

Magis

Earls

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear. Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.

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“…The largely sporadic nature of most ALS cases indicates that extrinsic factors, including diet, may play a relevant role in ALS, representing either a potential risk or a neuroprotective factor [ 141 ]. Growing evidence demonstrates that specific nutritional regimens [ 142 ] or dietary components [ 143 ] may influence the state of ALS patients or mouse models, by affecting at several levels (microbiome, mitochondrial activity, etc.) the pathological condition of high oxidative stress.…”

Section: Noncoding Rna Landscapementioning

confidence: 99%

RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective

Laneve

Tollis

Caffarelli

2021

IJMS

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RNA metabolism is central to cellular physiopathology. Almost all the molecular pathways underpinning biological processes are affected by the events governing the RNA life cycle, ranging from transcription to degradation. The deregulation of these processes contributes to the onset and progression of human diseases. In recent decades, considerable efforts have been devoted to the characterization of noncoding RNAs (ncRNAs) and to the study of their role in the homeostasis of the nervous system (NS), where they are highly enriched. Acting as major regulators of gene expression, ncRNAs orchestrate all the steps of the differentiation programs, participate in the mechanisms underlying neural functions, and are crucially implicated in the development of neuronal pathologies, among which are neurodegenerative diseases. This review aims to explore the link between ncRNA dysregulation and amyotrophic lateral sclerosis (ALS), the most frequent motoneuron (MN) disorder in adults. Notably, defective RNA metabolism is known to be largely associated with this pathology, which is often regarded as an RNA disease. We also discuss the potential role that these transcripts may play as diagnostic biomarkers and therapeutic targets.

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Omega-3 Hastens and Omega-6 Delays the Progression of Neuropathology in a Murine Model of Familial ALS

Cited by 10 publications

References 23 publications

Amyotrophic Lateral Sclerosis: A Diet Review

Amyotrophic Lateral Sclerosis: A Diet Review

Multiomic blood correlates of genetic risk identify presymptomatic disease alterations

RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective

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