A focus on homocysteine in autism.

Kałużna–Czaplińska, Joanna; Żurawicz, Ewa; Michalska, Monika; Rynkowski, Jacek

doi:10.18388/abp.2013_1963

Cited by 63 publications

(40 citation statements)

References 72 publications

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“…The first module also correlates with previous experimental findings in patients with ASD, that is, elevated homocysteine levels and oxidative tissue damage [Frye & James, ; Kałużna‐Czaplińska, Żurawicz, Michalska, & Rynkowski, ; Rose, Melnyk, Pavliv, et al, ; Rose, Melnyk, Trusty, et al, ], including hypomyelination due to excessive utilization of choline in remethylation processes [Steinfeld et al, ]. Thus, elevated levels of homocysteine might act as a false stimulatory molecule on n ‐Methyl‐ d ‐aspartic Acid glutamate receptors (MIM 138251), causing excitotoxicity, and subsequent apoptosis of nerve cells in the developing brain [Ramaekers, Sequeira, & Quadros, ].…”

Section: Discussionsupporting

confidence: 80%

Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach

et al. 2017

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Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim of our study was to develop and test a novel, unbiased, bioinformatics approach in order to identify links between ASD and disturbed cerebral metabolism by focusing on abnormal folate metabolism, which could foster patient stratification and novel therapeutic interventions. An unbiased, automatable, computational workflow interaction model was developed using available data from public databases. The interaction network model of ASD-associated genes with known cerebral expression and function (SFARI) and metabolic networks (MetScape), including connections to known metabolic substrates, metabolites and cofactors involving folates, was established. Intersection of bioinformatically created networks resulted in a limited amount of interaction modules pointing to common disturbed metabolic pathways, linking ASD to CFD. Two independent interaction modules (comprising three pathways) covering enzymes encoded by ASD-related genes and folate cofactors utilizing enzymes were generated. Module 1 suggested possible interference of CFD with serine and lysine metabolism, while module 2 identified correlations with purine metabolism and inosine monophosphate production. Since our approach was primarily conceived as a proof of principle, further amendments of the presented initial model are necessary to obtain additional actionable outcomes. Our modelling strategy identified not only previously known interactions supported by evidence-based analyses, but also novel plausible interactions, which could be validated in subsequent functional and/or clinical studies. Autism Res 2017, 10: 1424-1435. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 80%

Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach

et al. 2017

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“…Previous studies have revealed an association of hyper‐Hcy with several diseases, such as Alzheimer's disease, Parkinson's disease, and stroke . High levels of Hcy are also associated with neuropsychiatric disorders, including autism . Well‐controlled studies have demonstrated increased levels of Hcy in serum and urine in children with autism .…”

Section: Discussionmentioning

confidence: 99%

“…Hyper‐Hcy was shown to be linked with several diseases in the central nervous system, including Alzheimer's disease, Parkinson's disease, and stroke . Abnormally high levels of Hcy have also been observed in serum and urine samples of autistic children and are considered as a potential diagnostic marker for nutritional deficiency that is associated with improper functioning of autistic children . However, alteration of Hcy metabolism in ASD is not fully understood.…”

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confidence: 99%

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

Huang

Chen

Jiang

et al. 2019

Psychiatry Clin Neurosci

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Aim Abnormally high levels of homocysteine (Hcy) are associated with autism spectrum disorder. Betaine is a methyl group donor in Hcy metabolism, and is known to prevent noxious Hcy accumulation. This study explored whether betaine could influence Hcy metabolism in a mouse model of autism and ameliorate behavioral abnormalities. Methods Pregnant ICR mice were administered valproic acid (VPA) intraperitoneally on Embryonic Day 12.5. Serum Hcy concentrations in the offspring were measured by enzyme‐linked immunosorbent assay. Expressions of Hcy‐metabolism‐related enzymes, betaine‐Hcy methyltransferase, cystathionine β‐synthase, and methionine synthase, were measured by quantitative reverse transcription polymerase chain reaction and western blotting. Offspring were treated by either betaine or saline at the age of 8 weeks and serum Hcy concentrations were measured. Social behaviors were assessed by sniff‐duration test and three‐chamber test. Repetitive behavior was evaluated by marble‐burying test. Tail‐flick test was performed to measure nociceptive sensitivity. Results Prenatal VPA‐exposed mice showed significantly elevated Hcy concentrations and decreased betaine‐Hcy methyltransferase expression. Treatment with betaine could reduce Hcy level in VPA‐exposed mice, attenuate social impairment and repetitive behavior, and normalize nociceptive sensitivity in this model. Conclusion Betaine could ameliorate autism‐like features and play a beneficial role in a mouse autism model induced by prenatal VPA exposure.

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“…1 Deficiency in the expression of enzymes, such as cystathionine b-synthase and cystathionine g-lyase or their cofactors, may lead to abnormal accumulation of Hcy, which is characteristic of inherited diseases such as homocystinuria and cardiovascular abnormalities. 2 GSH is the most abundant intracellular non-protein thiol. The ratio of free GSH to its oxidized state glutathione disulfide (normally 4100 : 1) is an indicator for the corresponding enzyme activity and the redox state of the cell.…”

Section: Introductionmentioning

confidence: 99%

Design strategies of fluorescent probes for selective detection among biothiols

et al. 2015

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Simple thiol derivatives, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play key roles in biological processes, and the fluorescent probes to detect such thiols in vivo selectively with high sensitivity and fast response times are critical for understanding their numerous functions. However, the similar structures and reactivities of these thiols pose considerable challenges to the development of such probes. This review focuses on various strategies for the design of fluorescent probes for the selective detection of biothiols. We classify the fluorescent probes for discrimination among biothiols according to reaction types between the probes and thiols such as cyclization with aldehydes, conjugate addition-cyclization with acrylates, native chemical ligation, and aromatic substitution-rearrangement.

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A focus on homocysteine in autism.

Cited by 63 publications

References 72 publications

Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach

Identification of likely associations between cerebral folate deficiency and complex genetic‐ and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach

Betaine ameliorates prenatal valproic‐acid‐induced autism‐like behavioral abnormalities in mice by promoting homocysteine metabolism

Design strategies of fluorescent probes for selective detection among biothiols

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