Serum metabolomics study in a group of Parkinson's disease patients from northern India

Babu, G. Nagesh; Gupta, Manjeet; Paliwal, Vimal Kumar; Singh, Suruchi; Chatterji, Tanushri; Roy, Raja

doi:10.1016/j.cca.2018.02.022

Cited by 48 publications

(44 citation statements)

References 39 publications

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“…Finally, we found reports of increased serum formate levels in patients with inflammatory diseases (ulcerative colitis and Crohn’s disease [23]) and neurological diseases (amyotrophic lateral sclerosis [24] and Parkinson’s disease [25]) relative to healthy controls. Thus, the use of serum formate as a potential biomarker for cancers with high serum formate will need further consideration.…”

Section: Discussionmentioning

confidence: 99%

Stratification of cancer and diabetes based on circulating levels of formate and glucose

et al. 2019

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Background Serum and urine metabolites have been investigated for their use as cancer biomarkers. The specificity of candidate metabolites can be limited by the impact of other disorders on metabolite levels. In particular, the increasing incidence of obesity could become a significant confounding factor. Methods Here we developed a multinomial classifier for the stratification of cancer, obesity and healthy phenotypes based on circulating glucose and formate levels. We quantified the classifier performance from the retrospective analysis of samples from breast cancer, lung cancer, obese individuals and healthy controls. Results We discovered that circulating formate levels are significantly lower in breast and lung cancer patients than in healthy controls. However, the performance of a cancer classifier based on formate levels alone is limited because obese patients also have low serum formate levels. By introducing a multinomial classifier based on circulating glucose and formate levels, we were able to improve the classifier performance, reaching a true positive rate of 79% with a false positive rate of 8%. Conclusions Circulating formate is reduced in HER2+ breast cancer, non-small cell lung cancer and highly obese patients relative to healthy controls. Further studies are required to determine the relevance of these observations in other cancer types and diseases. Electronic supplementary material The online version of this article (10.1186/s40170-019-0195-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Stratification of cancer and diabetes based on circulating levels of formate and glucose

et al. 2019

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“…The latter is likely to exert a protective effect in oxidative diseases. Histidine and carnosine are active through the imidazole cycle of histidine molecule that helps in scavenging ROS [37,38]. Autophagy dysfunction exacerbates cellular stress generation and in turn, the increased ROS production triggers the alteration of both autophagy and apoptosis processes.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics

Tebani

Abily-Donval

Schmitz-Afonso

et al. 2019

IJMS

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Metabolic phenotyping is poised as a powerful and promising tool for biomarker discovery in inherited metabolic diseases. However, few studies applied this approach to mcopolysaccharidoses (MPS). Thus, this innovative functional approach may unveil comprehensive impairments in MPS biology. This study explores mcopolysaccharidosis VI (MPS VI) or Maroteaux–Lamy syndrome (OMIM #253200) which is an autosomal recessive lysosomal storage disease caused by the deficiency of arylsulfatase B enzyme. Urine samples were collected from 16 MPS VI patients and 66 healthy control individuals. Untargeted metabolomics analysis was applied using ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Furthermore, dermatan sulfate, amino acids, carnitine, and acylcarnitine profiles were quantified using liquid chromatography coupled to tandem mass spectrometry. Univariate analysis and multivariate data modeling were used for integrative analysis and discriminant metabolites selection. Pathway analysis was done to unveil impaired metabolism. The study revealed significant differential biochemical patterns using multivariate data modeling. Pathway analysis revealed that several major amino acid pathways were dysregulated in MPS VI. Integrative analysis of targeted and untargeted metabolomics data with in silico results yielded arginine-proline, histidine, and glutathione metabolism being the most affected. This study is one of the first metabolic phenotyping studies of MPS VI. The findings might shed light on molecular understanding of MPS pathophysiology to develop further MPS studies to enhance diagnosis and treatments of this rare condition.

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“…Studies also examined the peripheral BCAA levels in PD patients. When compared to healthy controls, PD participants displayed higher BCAA levels in the plasma [ 143 , 144 , 146 ], saliva [ 147 ], and urine [ 148 ]. In one study that explored the potential correlations of serum BCAAs and PD development, none of the serum BCAAs were associated with the likelihood of PD [ 149 ].…”

Section: Altered Bcaas Metabolism In Other Neurological Disordersmentioning

confidence: 99%

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

Jakher

Ahrens‐Nicklas

2020

IJMS

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Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by decreased activity of the branched-chain α-ketoacid dehydrogenase complex (BCKDC), which catalyzes the irreversible catabolism of branched-chain amino acids (BCAAs). Current management of this BCAA dyshomeostasis consists of dietary restriction of BCAAs and liver transplantation, which aims to partially restore functional BCKDC activity in the periphery. These treatments improve the circulating levels of BCAAs and significantly increase survival rates in MSUD patients. However, significant cognitive and psychiatric morbidities remain. Specifically, patients are at a higher lifetime risk for cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorder. Recent literature suggests that the neurological sequelae may be due to the brain-specific roles of BCAAs. This review will focus on the derangements of BCAAs observed in the brain of MSUD patients and will explore the potential mechanisms driving neurologic dysfunction. Finally, we will discuss recent evidence that implicates the relevance of BCAA metabolism in other neurological disorders. An understanding of the role of BCAAs in the central nervous system may facilitate future identification of novel therapeutic approaches in MSUD and a broad range of neurological disorders.

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Serum metabolomics study in a group of Parkinson's disease patients from northern India

Cited by 48 publications

References 39 publications

Stratification of cancer and diabetes based on circulating levels of formate and glucose

Stratification of cancer and diabetes based on circulating levels of formate and glucose

Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics

Brain Branched-Chain Amino Acids in Maple Syrup Urine Disease: Implications for Neurological Disorders

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