Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review

Ferri, Laura; Ajdinaj, Paola; Rispoli, Marianna Gabriella; Carrarini, Claudia; Barbone, Filomena; D’Ardes, Damiano; Capasso, Margherita; Muzio, Antonio Di; Cipollone, Francesco; Onofrj, Marco; Bonanni, Laura

doi:10.3390/biom11060867

Cited by 8 publications

(10 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, several epidemiological studies have suggested a link between diabetes and ALS. Interestingly, type 2 diabetes has been found to be protective against ALS in several populations but the molecular mechanisms underlying this neuroprotection remain unclear (Kioumourtzoglou et al, 2015 ; D’Ovidio et al, 2018 ; Wannarong and Ungprasert, 2020 ; Ferri et al, 2021 ). Another switch gene, MTRNR2L8, has been implicated in atherosclerotic stroke and it may be a therapeutic target and a diagnostic biomarker for stroke (Shen et al, 2019 ; Wong et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

Bottero

Santiago²,

Quinn³

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no modifying treatments available. The molecular mechanisms underpinning disease pathogenesis are not fully understood. Recent studies have employed co-expression networks to identify key genes, known as “switch genes”, responsible for dramatic transcriptional changes in the blood of ALS patients. In this study, we directly investigate the root cause of ALS by examining the changes in gene expression in motor neurons that degenerate in patients. Co-expression networks identified in ALS patients’ spinal cord motor neurons revealed 610 switch genes in seven independent microarrays. Switch genes were enriched in several pathways, including viral carcinogenesis, PI3K-Akt, focal adhesion, proteoglycans in cancer, colorectal cancer, and thyroid hormone signaling. Transcription factors ELK1 and GATA2 were identified as key master regulators of the switch genes. Protein-chemical network analysis identified valproic acid, cyclosporine, estradiol, acetaminophen, quercetin, and carbamazepine as potential therapeutics for ALS. Furthermore, the chemical analysis identified metals and organic compounds including, arsenic, copper, nickel, and benzo(a)pyrene as possible mediators of neurodegeneration. The identification of switch genes provides insights into previously unknown biological pathways associated with ALS.

show abstract

Section: Discussionmentioning

confidence: 99%

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

Bottero

Santiago²,

Quinn³

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The molecular mechanism behind the relation between T2D and ALS is not completely clear [ 161 ]. A possible explanation could be due to the known involvement of TAR DNA-binding protein 43 kDa (TDP-43) in T2D and ALS [ 177 , 178 ]. Indeed, TDP-43 is involved in the formation of cytoplasmatic aggregation in motor neurons and can also regulate glucose transport by TBC1 [ 179 , 180 ].…”

Section: Discussionmentioning

confidence: 99%

Amyotrophic Lateral Sclerosis: A Diet Review

D’Antona

Caramenti

Porro

et al. 2021

Foods

View full text Add to dashboard Cite

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.

show abstract

“…Studies examining whole-country registers in England, Sweden, Taiwan, and Denmark have shown that early DB (diagnosed before the age of 50 in Sweden and Denmark or 65 in Taiwan) is associated with increased ALS risk. [71][72][73][74][75] In addition, high HbA1c (indicating high blood glucose levels over a time period) is significantly associated with higher ALS mortality. 76 These data suggest that type-2 DB (DB2) would be associated with increased ALS risk.…”

Section: Insulin Is Impaired In Alsmentioning

confidence: 99%

“…76 These data suggest that type-2 DB (DB2) would be associated with increased ALS risk. However, there is strong country, regional, and single clinic evidence that late age DB is associated with decreased ALS risk, 72,74,75,[77][78][79][80][81][82] delayed onset, [83][84][85][86] and longer survival. 83,84 We explain this apparent paradox further below.…”

Section: Insulin Is Impaired In Alsmentioning

confidence: 99%

Insulin-Based Treatment for Amyotrophic Lateral Sclerosis

Rappoport¹

2022

Preprint

View full text Add to dashboard Cite

Background Amyotrophic Lateral Sclerosis (ALS) is a devastating disease involving motor neuron degeneration. The few drugs approved for treatment have at most a marginal benefit, and death usually occurs 2-5 years after diagnosis. Methods A thorough manual examination of the relevant literature, covering over 35,000 papers. Results Two major phenomena that are generally not known to clinicians were found. First, insulin signaling is impaired in ALS even in patients not diagnosed with diabetes (DB). Almost all studies that have explicitly tested insulin function in non-DB ALS patients using glucose tolerance tests (18 out of 20, 1964-2022, different groups) have found it to be impaired. Second, there is strong evidence for excessive insulin-independent glucose uptake (IIGU) in ALS. In addition, (i) early/late diabetes are associated with increased/decreased risk, respectively; (ii) insulin-based diabetes drugs are protective in ALS in large retrospective human studies; and (iii) strong animal and human evidence shows that insulin opposes all of the major pathological processes in ALS. Conclusion Most ALS patients have insulin impairment, yet this is commonly not diagnosed, likely because excessive IIGU normalizes glucose levels. The impairment promotes disease progression. Late diabetes is associated with decreased risk because high glucose levels indicate non-excessive IIGU, and because diabetes drugs are protective. Insulin-based treatment (e.g., GLP1 agonists, insulin) is beneficial and can be disease-modifying in ALS and in frontotemporal dementia variants comorbid with ALS. ALS patients should be routinely tested for insulin function and treated if test results are positive.

show abstract

Diabetes Mellitus and Amyotrophic Lateral Sclerosis: A Systematic Review

Cited by 8 publications

References 124 publications

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

Amyotrophic Lateral Sclerosis: A Diet Review

Insulin-Based Treatment for Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About