Amyotrophic lateral sclerosis (ALS) and the endocrine system: Are there any further ties to be explored?

Mentis, Alexios‐Fotios A.; Bougea, Anastasia; Chrousos, George P.

doi:10.1016/j.nbas.2021.100024

Cited by 7 publications

(5 citation statements)

References 167 publications

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“…In animal studies, prolonged exposure to high serum cortisol leads to irreversible hippocampal dysfunction [ 73 ]. In ALS, patients exhibited higher levels of a higher DHEAS/cortisol ratio and worse prognoses [ 74 ]. The alterations of cortisol and DHEA may subsequently affect the neuronal activity in the brain, but the underlying mechanisms remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Rat Hair Metabolomics Analysis Reveals Perturbations of Unsaturated Fatty Acid Biosynthesis, Phenylalanine, and Arachidonic Acid Metabolism Pathways Are Associated with Amyloid-β-Induced Cognitive Deficits

Tan

Chang

et al. 2023

Mol Neurobiol

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Hair is a noninvasive valuable biospecimen for the long-term assessment of endogenous metabolic disturbance. Whether the hair is suitable for identifying biomarkers of the Alzheimer’s disease (AD) process remains unknown. We aim to investigate the metabolism changes in hair after β-amyloid (Aβ1-42) exposure in rats using ultra-high-performance liquid chromatography-high-resolution mass spectrometry–based untargeted and targeted methods. Thirty-five days after Aβ1-42 induction, rats displayed significant cognitive deficits, and forty metabolites were changed, of which twenty belonged to three perturbed pathways: (1) phenylalanine metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis—l-phenylalanine, phenylpyruvate, ortho-hydroxyphenylacetic acid, and phenyllactic acid are up-regulated; (2) arachidonic acid (ARA) metabolism—leukotriene B4 (LTB4), arachidonyl carnitine, and 5(S)-HPETE are upregulation, but ARA, 14,15-DiHETrE, 5(S)-HETE, and PGB2 are opposite; and (3) unsaturated fatty acid biosynthesis— eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), FA 18:3 + 1O, and FA 18:3 + 2O are downregulated. Linoleic acid metabolism belonging to the biosynthesis of unsaturated fatty acid includes the upregulation of 8-hydroxy-9,10-epoxystearic acid, 13-oxoODE, and FA 18:2 + 4O, and downregulation of 9(S)-HPODE and dihomo-γ-linolenic acid. In addition, cortisone and dehydroepiandrosterone belonging to steroid hormone biosynthesis are upregulated. These three perturbed metabolic pathways also correlate with cognitive impairment after Aβ1-42 stimulation. Furthermore, ARA, DHA, EPA, l-phenylalanine, and cortisone have been previously implicated in the cerebrospinal fluid of AD patients and show a similar changing trend in Aβ1-42 rats’ hair. These data suggest hair can be a useful biospecimen that well reflects the expression of non-polar molecules under Aβ1-42 stimulation, and the five metabolites have the potential to serve as novel AD biomarkers.

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Section: Discussionmentioning

confidence: 99%

Rat Hair Metabolomics Analysis Reveals Perturbations of Unsaturated Fatty Acid Biosynthesis, Phenylalanine, and Arachidonic Acid Metabolism Pathways Are Associated with Amyloid-β-Induced Cognitive Deficits

Tan

Chang

et al. 2023

Mol Neurobiol

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“…As ALS deteriorates, particularly in the growing elderly population, it is important to address potential comorbidities. 58 It seems crucial for future studies involving multiple centers should investigate the connection between ALS and the endocrine system in larger groups of patients. Furthermore, future research should focus on the neuropsychological situation experienced by patients with ALS and its impact on the hypothalamic nuclei.…”

Section: Limitations and Recommendationsmentioning

confidence: 99%

“…Exploring the issue of volume loss in the hypothalamic subunit should be considered in patients with ALS to reduce the impact of the disease. As ALS deteriorates, particularly in the growing elderly population, it is important to address potential comorbidities 58 . It seems crucial for future studies involving multiple centers should investigate the connection between ALS and the endocrine system in larger groups of patients.…”

Section: Limitations and Recommendationsmentioning

confidence: 99%

Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis

Ghaderi,

Fatehi,

Kalra

et al. 2024

CNS Neurosci Ther

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Background and ObjectiveAmyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non‐motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features.MethodsForty‐eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior‐superior (a‐sHyp), anterior‐inferior (a‐iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t‐tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables.ResultsThe volume of the left a‐sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = ‐0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS‐R in patients with ALS. However, right a‐sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = −0.471, p = 0.020) and left postHyp (r = −0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS‐R) scores ≤41 and >41 and those with a disease duration of 9 months or less.Discussion and ConclusionThe main finding suggests atrophy of the left a‐sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra‐motor neuroimaging finding for ALS.

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“…The remaining 10% of ALS cases are of the familial type ( C9orf72, CHCHD10, SQSTM1, and the TBK1 gene). A schematic representation of muscle dysfunction and ALS pathology is depicted in Figure 5 [ 138 ].…”

Section: Types Of Brain Disordersmentioning

confidence: 99%

Mechanistic Insights, Treatment Paradigms, and Clinical Progress in Neurological Disorders: Current and Future Prospects

Alkahtani

AL–Johani

Alarifi

2023

IJMS

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Neurodegenerative diseases (NDs) are a major cause of disability and are related to brain development. The neurological signs of brain lesions can vary from mild clinical shortfalls to more delicate and severe neurological/behavioral symptoms and learning disabilities, which are progressive. In this paper, we have tried to summarize a collective view of various NDs and their possible therapeutic outcomes. These diseases often occur as a consequence of the misfolding of proteins post-translation, as well as the dysfunctional trafficking of proteins. In the treatment of neurological disorders, a challenging hurdle to cross regarding drug delivery is the blood–brain barrier (BBB). The BBB plays a unique role in maintaining the homeostasis of the central nervous system (CNS) by exchanging components between the circulations and shielding the brain from neurotoxic pathogens and detrimental compounds. Here, we outline the current knowledge about BBB deterioration in the evolving brain, its origin, and therapeutic interventions. Additionally, we summarize the physiological scenarios of the BBB and its role in various cerebrovascular diseases. Overall, this information provides a detailed account of BBB functioning and the development of relevant treatments for neurological disorders. This paper will definitely help readers working in the field of neurological scientific communities.

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Amyotrophic lateral sclerosis (ALS) and the endocrine system: Are there any further ties to be explored?

Cited by 7 publications

References 167 publications

Rat Hair Metabolomics Analysis Reveals Perturbations of Unsaturated Fatty Acid Biosynthesis, Phenylalanine, and Arachidonic Acid Metabolism Pathways Are Associated with Amyloid-β-Induced Cognitive Deficits

Rat Hair Metabolomics Analysis Reveals Perturbations of Unsaturated Fatty Acid Biosynthesis, Phenylalanine, and Arachidonic Acid Metabolism Pathways Are Associated with Amyloid-β-Induced Cognitive Deficits

Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis

Mechanistic Insights, Treatment Paradigms, and Clinical Progress in Neurological Disorders: Current and Future Prospects

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