Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression

Ioannides, Zara A.; Ngo, Shyuan T.; Henderson, Robert D.; McCombe, Pamela A.; Steyn, Frederik J.

doi:10.1159/000446502

Cited by 50 publications

(42 citation statements)

References 176 publications

(220 reference statements)

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“…Risk factors discussed are both physical trauma and chemicals. Confounders such as head trauma (in the case of Gulf veterans and professional athletes) and increased metabolism [103] caused by heavy physical work and agricultural work also might have an impact on the risk for ALS.…”

Section: Discussionmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses

Gunnarsson

Bodin

2018

IJERPH

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Objectives: We conducted a systematic literature review to identify studies fulfilling good scientific epidemiological standards for use in meta-analyses of occupational risk factors for amyotrophic lateral sclerosis (ALS). Methods: We identified 79 original publications on associations between work and ALS. The MOOSE (Meta-analysis Of Observational Studies in Epidemiology) and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) guidelines were used to ensure high scientific quality, and reliable protocols were applied to classify the articles. Thirty-seven articles fulfilled good scientific standards, while 42 were methodologically deficient and thus were excluded from our meta-analyses. Results: The weighted relative risks for the various occupational exposures were respectively; 1.29 (95% confidence interval (CI): 0.97–1.72; six articles) for heavy physical work, 3.98 (95% CI: 2.04–7.77; three articles) for professional sports, 1.45 (95% CI: 1.07–1.96; six articles) for metals, 1.19 (95% CI: 1.07–1.33; 10 articles) for chemicals, 1.18 (95% CI: 1.07–1.31; 16 articles) for electromagnetic fields or working with electricity, and 1.18 (95% CI: 1.05–1.34; four articles) for working as a nurse or physician. Conclusions: Meta-analyses based only on epidemiologic publications of good scientific quality show that the risk of ALS is statistically significantly elevated for occupational exposures to excessive physical work, chemicals (especially pesticides), metals (especially lead), and possibly also to electromagnetic fields and health care work. These results are not explained by publication bias.

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Section: Discussionmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses

Gunnarsson

Bodin

2018

IJERPH

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“…Several mechanisms contribute to altered energy balance in ALS from decreased energy supply and fat storage to increased energy expenditure (reviewed in [18]), but globally, these features appear to affect disease progression more than onset [18]. No influence of riluzole treatment on APN levels has been previously reported [32].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, energy metabolism is impaired in both sporadic (sALS) and familiar ALS (fALS) patients [12, 17]. Hypermetabolism, weight loss, hyperlipidaemia and impaired glucose tolerance have been reported in ALS [17], although they are apparently related to advanced disease severity [18]. In fact, inclusions of TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein) characterize most of ALS brain tissues whereas the naïve protein regulates fat deposition and glucose pathway [12, 19].…”

Section: Introductionmentioning

confidence: 99%

Adiponectin levels in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients: possible influence on neuroinflammation?

Bossolasco

Cancello

Doretti

et al. 2017

J Neuroinflammation

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BackgroundAdiponectin (APN) is a key player in energy homeostasis strictly associated with cerebrovascular and neurodegenerative diseases. Since APN also belongs to anti-inflammatory-acting adipokines and may influence both neuroinflammation and neurodegenerative processes, we decided to study the APN levels in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases.MethodsWe assessed APN levels by ELISA immunoassay in both the serum and cerebrospinal fluid of a cohort of familial and sporadic ALS patients, characterized by normal body mass index and absence of dysautonomic symptoms. The screening of serum APN levels was also performed in patients affected by other neurological disorders, including fronto-temporal dementia (FTD) patients. Means were compared using the non-parametric Wilcoxon test, and Pearson’s or Spearman’s rho was used to assess correlations between variables.ResultsIn the whole ALS group, serum APN levels were not different when compared to the age- and sex-matched control group (CTR), but a gender-specific analysis enlightened a significant opposite APN trend between ALS males, characterized by lower values (ALS 9.8 ± 5.2 vs. CTR 15 ± 9.7 μg/ml), and ALS females, showing higher amounts (ALS 26.5 ± 11.6 vs. CTR 14.6 ± 5.2 μg/ml). This sex-linked difference was significantly enhanced in familial ALS cases (p ≤ 0.01). The APN levels in ALS cerebrospinal fluids were unrelated to serum values and not linked to sex and/or familiarity of the disease. Finally, the screening of serum APN levels in patients affected by other neurological disorders revealed the highest serum values in FTD patients.ConclusionsOpposite serum APN levels are gender-related in ALS and altered in several neurological disorders, with the highest values in FTD, which shares with ALS several overlapping and neuropathological features. Further investigations are needed to clarify the possible involvement of APN in neuroinflammation and neurodegeneration.Graphical AbstractPossible involvement of APN in neuroinflammatory neurodegenerative diseases

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“…Impaired bioenergetics in the brain of HD and PD patients especially affects basal ganglia (Amano et al 2015) while energy deficit seems to commence in the precuneus and spread to other parts of the cerebral cortex in AD (Love and Miners 2016). In addition, a state of chronic energy deficit in the motor cortex has been reported in ALS (Ioannides et al 2016). Several recent reviews described possible therapeutic advances in targeting mitochondrial bioenergetics in neurodegeneration (Yao and Brinton 2011;Yadav et al 2014).…”

Section: Energy Deficit and Neurodegenerationmentioning

confidence: 99%

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

Ostojić

2017

Tohoku J. Exp. Med.

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Mitochondrial energy deficit is considered a key element of different clinical pathologies -from inherited disorders of energy metabolism to drug-induced mitochondrial toxicity, to cardiometabolic and neurodegenerative diseases. However, clinical manifestations of impaired bioenergetics are not easy to recognize, with patient-reported features usually include non-pathognomonic fatigue and weakness, or exercise intolerance, while specific lab tests are missing. Although it is not clear whether poor energetics is a primary deficit or a secondary consequence of specific disorders, improving mitochondrial viability remains a challenging task in both experimental and clinical medicine. In this review, biochemical and clinical evidence of energy deficits were reviewed, along with possible therapeutic options to tackle energy failure and restore bioenergetics.

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Altered Metabolic Homeostasis in Amyotrophic Lateral Sclerosis: Mechanisms of Energy Imbalance and Contribution to Disease Progression

Cited by 50 publications

References 176 publications

Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses

Amyotrophic Lateral Sclerosis and Occupational Exposures: A Systematic Literature Review and Meta-Analyses

Adiponectin levels in the serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients: possible influence on neuroinflammation?

Impaired Bioenergetics in Clinical Medicine: A Target to Tackle

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