[P4–435]: Non‐equilibrium Phase Transition in Biochemical Systems: Chain of Chirality Transfer as Determinant of Brain Functional Laterality — Relevance to Alzheimer Disease and Cognitive Psychology

Dyakin, Victor Vasilievich; Lucas, Justin

doi:10.1016/j.jalz.2017.07.595

Cited by 4 publications

(7 citation statements)

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“…Currently accumulated data about PTMs of many proteins and peptides, including Aβ are coherent with the silently accepted racemization hypothesis of protein aggregation (RHPA). Therefore, after "three decades of struggles, ACH [46] of the neurodegeneration should be complemented by the concept of PTMs Sp and non-equilibrium phase transitions (PhTs NE ) [47][48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Chiral Interface of Amyloid Beta (Aβ): Relevance to Protein Aging, Aggregation and Neurodegeneration

2020

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Biochirality is the subject of distinct branches of science, including biophysics, biochemistry, the stereochemistry of protein folding, neuroscience, brain functional laterality and bioinformatics. At the protein level, biochirality is closely associated with various post-translational modifications (PTMs) accompanied by the non-equilibrium phase transitions (PhTs NE ). PTMs NE support the dynamic balance of the prevalent chirality of enzymes and their substrates. The stereoselective nature of most biochemical reactions is evident in the enzymatic (Enz) and spontaneous (Sp) PTMs (PTMs Enz and PTMs Sp ) of proteins. Protein chirality, which embraces biophysics and biochemistry, is a subject of this review. In this broad field, we focus attention to the amyloid-beta (Aβ) peptide, known for its essential cellular functions and associations with neuropathology. The widely discussed amyloid cascade hypothesis (ACH) of Alzheimer's disease (AD) states that disease pathogenesis is initiated by the oligomerization and subsequent aggregation of the Aβ peptide into plaques. The racemization-induced aggregation of protein and RNA have been extensively studied in the search for the contribution of spontaneous stochastic stereo-specific mechanisms that are common for both kinds of biomolecules. The failure of numerous Aβ drug-targeting therapies requires the reconsolidation of the ACH with the concept of PTMs Sp . The progress in methods of chiral discrimination can help overcome previous limitations in the understanding of AD pathogenesis. The primary target of attention becomes the network of stereospecific PTMs that affect the aggregation of many pathogenic agents, including Aβ. Extensive recent experimental results describe the truncated, isomerized and racemized forms of Aβ and the interplay between enzymatic and PTMs Sp . Currently, accumulated data suggest that non-enzymatic PTMs Sp occur in parallel to an existing metabolic network of enzymatic pathways, meaning that the presence and activity of enzymes does not prevent non-enzymatic reactions from occurring. PTMs Sp impact the functions of many proteins and peptides, including Aβ. This is in logical agreement with the silently accepted racemization hypothesis of protein aggregation (RHPA). Therefore, the ACH of AD should be complemented by the concept of PTMs Sp and RHPA.

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Section: Discussionmentioning

confidence: 99%

Chiral Interface of Amyloid Beta (Aβ): Relevance to Protein Aging, Aggregation and Neurodegeneration

2020

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“…1996]. Consequently, it was found that molecular chirality is a determining factor in the external and internal symmetry of non-organic crystals and biological macromolecules, including proteins lipids, and DNA, [Dyakin, et al 2017]. From a different perspective, an increasing line of convincing evidence suggests that stereo-specific chemical evolution may originate before the origin of terrestrial life from the contribution of the symmetry patterns of the macroscale galaxy dynamics [Cline, 2010: Takahashi & Kobayashi, 2019.…”

Section: Fragile Space-time Symmetrymentioning

confidence: 99%

“…The common belief that molecular chirality is a central feature in the origin and evolution of biological systems is reflected in many reviews [Keszthelyi. 2009;Dyakin, et al 2017-A, Barron, 2021Wang, 2022]. The emergence of chirality of life, is associated with the break of symmetry at the molecular level.…”

Section: Hierarchical Levelsmentioning

confidence: 99%

Fundamental Cause of Bio-Chirality - Space-Time Symmetry: Concept Review

Dyakin¹

2022

Preprint

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The search for fundamental determinants of bio-molecular chirality is a hot topic in biology, clarifying the meaning of evolution and the enigma of life's origin. Non-biological and biological entities obey the universal laws of nature grounded on space-time symmetry (STS) transformations. The fabric of STS is the immense subject of our review. The symmetry, encompassing behavior of elementary particles and galaxy structure, imposes its fundamental laws on all hierarchical levels of the biological world. Objects across spatial scales may be classified as chiral or achiral concerning a specific space-related symmetry transformation - mirror reflection. Chirality as a symmetry element reflecting the property of asymmetry (or dissymmetry) is the critical structural feature of natural systems, including sub-atomic particles and living matter. The inheritance of molecular symmetry from the symmetry of elementary particles points to the bi-directional causal pathway of prevalent bio-chirality. We assume that both extremities of spatial dimension naturally influence this transitional state of biological matter. The current review promotes an integrative holistic approach to the new experimental results in fast-developing and divergent branches of STS and biological chirality. The generalized view on biological chirality is a necessary and promising avenue for adequately understanding the link between protein folding, cell morphology, neuronal signaling, and laterality of cognitive functions.

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“…The endocrine and immune systems exhibit age-related alterations [ 3 , 104 ] and the asymmetry in the activity of corresponding brain regions have a long history of experimental observation [ 105 ]. Still, their relation to protein homochirality, spontaneous PTMs, and left/right brain asymmetry is not sufficiently understood even though the link between two poles of this phenomenon–morphological bilaterality/handedness [ 106 , 107 , 108 ] and prevalent molecular chirality [ 82 , 109 , 110 , 111 , 112 ] gain significant advances in recent decades. The association of the SRS with the physiological and pathological molecular chirality is the subject of our specific attention.…”

Section: Crosstalk Of Physiological and Psychological Statesmentioning

confidence: 99%

“…Stress-induced, age-associated deterioration of cognition and psychological functions correlates with neuronal degeneration, misfolding, disfunction, and aggregation of synapse-associated proteins and peptides, including NMDA receptors, A-β, TAU, neuroligins, neurexins, and many others [ 97 ]. An emerging concept proposes that molecular and sub-cellular structures “sense, integrate, and transduce psychosocial and behavioral factors”, suggesting the reciprocal causation between age-associated molecular, cognitive and psychological factors [ 55 , 78 , 99 , 100 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ]. The psychological perspective of aging, seeing through molecular and cell biology prism, helps better understand the complex interrelationships among protein folding, cell signaling, brain structure, cognition, and behavior for both healthy and pathological trajectories [ 122 , 123 ].…”

Section: Crosstalk Of Physiological and Psychological Statesmentioning

confidence: 99%

Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

Dyakin

Dyakina-Fagnano

McIntire

et al. 2021

IJMS

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In humans, age-associated degrading changes, widely observed in molecular and cellular processes underly the time-dependent decline in spatial navigation, time perception, cognitive and psychological abilities, and memory. Cross-talk of biological, cognitive, and psychological clocks provides an integrative contribution to healthy and advanced aging. At the molecular level, genome, proteome, and lipidome instability are widely recognized as the primary causal factors in aging. We narrow attention to the roles of protein aging linked to prevalent amino acids chirality, enzymatic and spontaneous (non-enzymatic) post-translational modifications (PTMs SP), and non-equilibrium phase transitions. The homochirality of protein synthesis, resulting in the steady-state non-equilibrium condition of protein structure, makes them prone to multiple types of enzymatic and spontaneous PTMs, including racemization and isomerization. Spontaneous racemization leads to the loss of the balanced prevalent chirality. Advanced biological aging related to irreversible PTMs SP has been associated with the nontrivial interplay between somatic (molecular aging) and mental (psychological aging) health conditions. Through stress response systems (SRS), the environmental and psychological stressors contribute to the age-associated “collapse” of protein homochirality. The role of prevalent protein chirality and entropy of protein folding in biological aging is mainly overlooked. In a more generalized context, the time-dependent shift from enzymatic to the non-enzymatic transformation of biochirality might represent an important and yet underappreciated hallmark of aging. We provide the experimental arguments in support of the racemization theory of aging.

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[P4–435]: Non‐equilibrium Phase Transition in Biochemical Systems: Chain of Chirality Transfer as Determinant of Brain Functional Laterality — Relevance to Alzheimer Disease and Cognitive Psychology

Cited by 4 publications

References 0 publications

Chiral Interface of Amyloid Beta (Aβ): Relevance to Protein Aging, Aggregation and Neurodegeneration

Chiral Interface of Amyloid Beta (Aβ): Relevance to Protein Aging, Aggregation and Neurodegeneration

Fundamental Cause of Bio-Chirality - Space-Time Symmetry: Concept Review

Fundamental Clock of Biological Aging: Convergence of Molecular, Neurodegenerative, Cognitive and Psychiatric Pathways: Non-Equilibrium Thermodynamics Meet Psychology

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