The Chain of Chirality Transfer as Determinant of Brain Functional Laterality. Breaking the Chirality Silence: Search for New Generation of Biomarkers; Relevance to Neurodegenerative Diseases, Cognitive Psychology, and Nutrition Science

Dyakin, Victor V.; Lucas, Justin; Dyakina‐Fagnano, Nika Victorovna; Posner, Eva V.; Vadász, Csaba

doi:10.24983/scitemed.nnr.2017.00028

Cited by 10 publications

(9 citation statements)

References 190 publications

(248 reference statements)

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“…Although the VCT images were contrast-enhanced, hippocampal morphology and their boundaries remained subject to visual interpretation by the readers. Bi-laterality and hemispheric asymmetry are widely recognized as the indispensable evolutionally conserved attributes of the brain [ 33 ]. In particular, the hemispheric asymmetry of the healthy human hippocampus is well established [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Hyperplanar Morphological Clustering of a Hippocampus by Using Volumetric Computerized Tomography in Early Alzheimer’s Disease

Suksuphew

Horkaew

2017

Brain Sciences

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Background: On diagnosing Alzheimer’s disease (AD), most existing imaging-based schemes have relied on analyzing the hippocampus and its peripheral structures. Recent studies have confirmed that volumetric variations are one of the primary indicators in differentiating symptomatic AD from healthy aging. In this study, we focused on deriving discriminative shape-based parameters that could effectively identify early AD from volumetric computerized tomography (VCT) delineation, which was previously almost intangible. Methods: Participants were 63 volunteers of Thai nationality, whose ages were between 40 and 90 years old. Thirty subjects (age 68.51 ± 5.5) were diagnosed with early AD, by using Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria and the National Institute of Neurological and Communicative Disorders and the Stroke and the Alzheimer’s disease and Related Disorders Association (NINCDS-ADRDA) criteria, while the remaining 33 were in the healthy control group (age 67.93 ± 5.5). The structural imaging study was conducted by using VCT. Three uninformed readers were asked to draw left and right hippocampal outlines on a coronal section. The resultant shapes were aligned and then analyzed with statistical shape analysis to obtain the first few dominant variational parameters, residing in hyperplanes. A supervised machine learning, i.e., support vector machine (SVM) was then employed to elucidate the proposed scheme. Results: Provided trivial delineations, relatively as low as 5 to 7 implicit model parameters could be extracted and used as discriminants. Clinical verification showed that the model could differentiate early AD from aging, with high sensitivity, specificity, accuracy and F-measure of 0.970, 0.968, 0.983 and 0.983, respectively, with no apparent effect of left-right asymmetry. Thanks to a less laborious task required, yet high discriminating capability, the proposed scheme is expected to be applicable in a typical clinical setting, equipped with only a moderate-specs VCT.

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Section: Discussionmentioning

confidence: 99%

Hyperplanar Morphological Clustering of a Hippocampus by Using Volumetric Computerized Tomography in Early Alzheimer’s Disease

Suksuphew

Horkaew

2017

Brain Sciences

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“…The morphological brain asymmetry correlates with cognitive functions [ 437 , 438 ]. A chain of lateralization is believed to originate from genetic as well as from epigenetic impact [ 21 , 439 ].…”

Section: Racemization Role At Molecular Cellular and System (Organ) Levelsmentioning

confidence: 99%

“…The transport of proteins from the cytosol to the membrane phosphor-lipid or nuclear environment is accompanied by conformational phase transitions. The interplay of the thermodynamic equilibrium and the fundamentally non-equilibrium nature of cellular biochemistry constitutes the basis for the non-equilibrium phase transitions [ 21 , 22 , 33 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

“…Comparative measurements show that most D-AAs present in the hippocampus are significantly higher in the cortex. Regardless of brain region, the changes in AA chirality cause changes in protein structures (chirality transfer) including forming alpha-helical and beta-sheet structures resulting in changes in metabolic activity and function [ 19 , 21 , 131 ]. All changes in protein synthesis and degradation are accompanied by sequential spatial (chirality-dependent) transformations.…”

Section: Introductionmentioning

confidence: 99%

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Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg

2021

Self Cite

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Homochirality of DNA and prevalent chirality of free and protein-bound amino acids in a living organism represents the challenge for modern biochemistry and neuroscience. The idea of an association between age-related disease, neurodegeneration, and racemization originated from the studies of fossils and cataract disease. Under the pressure of new results, this concept has a broader significance linking protein folding, aggregation, and disfunction to an organism’s cognitive and behavioral functions. The integrity of cognitive function is provided by a delicate balance between the evolutionarily imposed molecular homo-chirality and the epigenetic/developmental impact of spontaneous and enzymatic racemization. The chirality of amino acids is the crucial player in the modulation the structure and function of proteins, lipids, and DNA. The collapse of homochirality by racemization is the result of the conformational phase transition. The racemization of protein-bound amino acids (spontaneous and enzymatic) occurs through thermal activation over the energy barrier or by the tunnel transfer effect under the energy barrier. The phase transition is achieved through the intermediate state, where the chirality of alpha carbon vanished. From a thermodynamic consideration, the system in the homo-chiral (single enantiomeric) state is characterized by a decreased level of entropy. The oscillating protein chirality is suggesting its distinct significance in the neurotransmission and flow of perceptual information, adaptive associative learning, and cognitive laterality. The common pathological hallmarks of neurodegenerative disorders include protein misfolding, aging, and the deposition of protease-resistant protein aggregates. Each of the landmarks is influenced by racemization. The brain region, cell type, and age-dependent racemization critically influence the functions of many intracellular, membrane-bound, and extracellular proteins including amyloid precursor protein (APP), TAU, PrP, Huntingtin, α-synuclein, myelin basic protein (MBP), and collagen. The amyloid cascade hypothesis in Alzheimer’s disease (AD) coexists with the failure of amyloid beta (Aβ) targeting drug therapy. According to our view, racemization should be considered as a critical factor of protein conformation with the potential for inducing order, disorder, misfolding, aggregation, toxicity, and malfunctions.

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“…Molecular chirality has been found to affect protein folding, neuronal proliferation, and brain functional laterality and plays an important role in cognition, behavior, and psychiatry [16]. Previous studies reported enantiomers may differ from one another markedly because of different pharmacodynamics and pharmacokinetic properties [17].…”

Section: Introductionmentioning

confidence: 99%

d-glutamate and Gut Microbiota in Alzheimer’s Disease

Chang

Lin

Lane

2020

IJMS

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Background: An increasing number of studies have shown that the brain–gut–microbiota axis may significantly contribute to Alzheimer’s disease (AD) pathogenesis. Moreover, impaired memory and learning involve the dysfunction neurotransmission of glutamate, the agonist of the N-methyl-d-aspartate receptor and a major excitatory neurotransmitter in the brain. This systematic review aimed to summarize the current cutting-edge research on the gut microbiota and glutamate alterations associated with dementia. Methods: PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, and Cochrane Systematic Reviews were reviewed for all studies on glutamate and gut microbiota in dementia published up until Feb 2020. Results: Several pilot studies have reported alterations of gut microbiota and metabolites in AD patients and other forms of dementia. Gut microbiota including Bacteroides vulgatus and Campylobacter jejuni affect glutamate metabolism and decrease the glutamate metabolite 2-keto-glutaramic acid. Meanwhile, gut bacteria with glutamate racemase including Corynebacterium glutamicum, Brevibacterium lactofermentum, and Brevibacterium avium can convert l-glutamate to d-glutamate. N-methyl-d-aspartate glutamate receptor (NMDAR)-enhancing agents have been found to potentially improve cognition in AD or Parkinson’s disease patients. These findings suggest that d-glutamate (d-form glutamate) metabolized by the gut bacteria may influence the glutamate NMDAR and cognitive function in dementia patients. Conclusions: Gut microbiota and glutamate are potential novel interventions to be developed for dementia. Exploring comprehensive cognitive functions in animal and human trials with glutamate-related NMDAR enhancers are warranted to examine d-glutamate signaling efficacy in gut microbiota in patients with AD and other neurodegenerative dementias.

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The Chain of Chirality Transfer as Determinant of Brain Functional Laterality. Breaking the Chirality Silence: Search for New Generation of Biomarkers; Relevance to Neurodegenerative Diseases, Cognitive Psychology, and Nutrition Science

Cited by 10 publications

References 190 publications

Hyperplanar Morphological Clustering of a Hippocampus by Using Volumetric Computerized Tomography in Early Alzheimer’s Disease

Hyperplanar Morphological Clustering of a Hippocampus by Using Volumetric Computerized Tomography in Early Alzheimer’s Disease

Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg

d-glutamate and Gut Microbiota in Alzheimer’s Disease

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