Exothermic transitions in the heat capacity profiles of human cerebrospinal fluid

Antonova, Borislava; Naydenov, E.; Koynova, Rumiana; Tumangelova-Yuzeir, Kalina; Tenchov, Boris

doi:10.1007/s00249-020-01429-w

Cited by 7 publications

(7 citation statements)

References 42 publications

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“…This biophysical technique is classically applied to study and thermodynamically describe the stability and conformational transitions of biomolecules in solution. However, DSC is also suitable to analyze complex biofluids such as blood plasma/serum [ 3 , 4 , 5 ], cerebrospinal fluid [ 6 , 7 ], and synovial fluid [ 8 ], the calorimetric profiles (thermograms or scans) of which are a complex mixture of the thermal transitions of the individual biofluid components. DSC profiles depend not only on the plasma/serum proteins content and conformation but also on factors that moderate their stability such as ligand binding, macromolecular complex formation, mutations, chemical changes, protein oligomerization, aggregation and misfolding.…”

Section: Application Of Differential Scanning Calorimetry For Plasma/...mentioning

confidence: 99%

Calorimetric Markers for Detection and Monitoring of Multiple Myeloma

Krumova

Todinova

Taneva

2022

Cancers

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This review summarizes data obtained thus far on the application of differential scanning calorimetry (DSC) for the analysis of blood sera from patients diagnosed with multiple myeloma (MM) with the secretion of the most common isotypes of monoclonal proteins (M-proteins), free light chains (FLC) and non-secretory MM, as well as Waldenström macroglobulinemia and the premalignant state monoclonal gammopathy of undetermined significance. The heterogeneous nature of MM is reflected in the thermal stability profiles of the blood serum proteome of MM patients found to depend on both the level and the isotype of the secreted M-proteins or FLC. Common calorimetric markers feature the vast majority of the different myeloma types, i.e., stabilization of the major serum proteins and decrease in the albumin/globulin heat capacity ratio. A unique calorimetric fingerprint of FLC molecules forming amorphous aggregates is the low-temperature transition centered at 57 °C for a calorimetric set of FLC MM and at 46–47 °C for a single FLC MM case for which larger aggregates were formed. The calorimetric assay proved particularly advantageous for non-secretory MM and is thus a suitable tool for monitoring such patients during treatment courses. Thus, DSC provides a promising blood-based approach as a complementary tool for MM detection and monitoring.

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Section: Application Of Differential Scanning Calorimetry For Plasma/...mentioning

confidence: 99%

Calorimetric Markers for Detection and Monitoring of Multiple Myeloma

Krumova

Todinova

Taneva

2022

Cancers

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“…Over the last decade, DSC has been applied in investigation of complex biofluids such as blood plasma/sera [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50], cerebrospinal fluid [51,52], cancer cells and nuclei [53], and brain tissue [54]. Farkas et al [55,56] have demonstrated that DSC can well be used to extract information on drug effects on blood plasma and RBCs [55,56] as well as on F and G actin in polyneuropathy [57].…”

Section: Discussionmentioning

confidence: 99%

Red Blood Cells’ Thermodynamic Behavior in Neurodegenerative Pathologies and Aging

et al. 2021

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The main trend of current research in neurodegenerative diseases (NDDs) is directed towards the discovery of novel biomarkers for disease diagnostics and progression. The pathological features of NDDs suggest that diagnostic markers can be found in peripheral fluids and cells. Herein, we investigated the thermodynamic behavior of the peripheral red blood cells (RBCs) derived from patients diagnosed with three common NDDs—Parkinson′s disease (PD), Alzheimer′s disease (AD), and amyotrophic lateral sclerosis (ALS) and compared it with that of healthy individuals, evaluating both fresh and aged RBCs. We established that NDDs can be differentiated from the normal healthy state on the basis of the variation in the thermodynamic parameters of the unfolding of major RBCs proteins—the cytoplasmic hemoglobin (Hb) and the membrane Band 3 (B3) protein. A common feature of NDDs is the higher thermal stability of both Hb and B3 proteins along the RBCs aging, while the calorimetric enthalpy can distinguish PD from ALS and AD. Our data provide insights into the RBCs thermodynamic behavior in two complex and tightly related phenomena—neurodegenerative pathologies and aging, and it suggests that the determined thermodynamic parameters are fingerprints of the altered conformation of Hb and B3 protein and modified RBCs’ aging in the studied NDDs.

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“…These reversible exothermic transitions vary depending on neurodegenerative pathologies and possibly reflect processes of protein fibrillization and/or aggregation. 49 , 50 Further, it has become clear that IDPs such as α-synuclein and tau protein are common among neurodegenerative diseases, especially Parkinson’s disease. It has been recognized that α-synuclein can form amyloid fibrils, which are implicated with the pathogenesis of Parkinson’s disease and other neurodegenerative conditions, collectively termed synucleinopathies.…”

Section: Intrinsically Disordered Proteinsmentioning

confidence: 99%

“…As a matter of fact, many proteins which are associated with neurodegeneration, diabetes, cardiovascular disease, amyloidosis, and genetic diseases, as well as the majority of the human cancer-related proteins, are either IDPs or contain long IDRs. − Recently, IDPs were suggested to be responsible for exothermic events observed in cerebrospinal fluid and brain proteome. These reversible exothermic transitions vary depending on neurodegenerative pathologies and possibly reflect processes of protein fibrillization and/or aggregation. , Further, it has become clear that IDPs such as α-synuclein and tau protein are common among neurodegenerative diseases, especially Parkinson’s disease. It has been recognized that α-synuclein can form amyloid fibrils, which are implicated with the pathogenesis of Parkinson’s disease and other neurodegenerative conditions, collectively termed synucleinopathies .…”

Section: Intrinsically Disordered Proteinsmentioning

confidence: 99%

Intrinsically Disordered Proteins: Perspective on COVID-19 Infection and Drug Discovery

Tenchov

Zhou

2022

ACS Infect. Dis.

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Since the beginning of the COVID-19 pandemic caused by SARS-CoV-2, millions of patients have been diagnosed and many of them have died from the disease worldwide. The identification of novel therapeutic targets are of utmost significance for prevention and treatment of COVID-19. SARS-CoV-2 is a single-stranded RNA virus with a 30 kb genome packaged into a membrane-enveloped virion, transcribing several tens of proteins. The belief that the amino acid sequence of proteins determines their 3D structure which, in turn, determines their function has been a central principle of molecular biology for a long time. Recently, it has been increasingly realized, however, that there is a large group of proteins that lack a fixed or ordered 3D structure, yet they exhibit important biological activities—so-called intrinsically disordered proteins and protein regions (IDPs/IDRs). Disordered regions in viral proteins are generally associated with viral infectivity and pathogenicity because they endow the viral proteins the ability to easily and promiscuously bind to host proteins; therefore, the proteome of SARS-CoV-2 has been thoroughly examined for intrinsic disorder. It has been recognized that, in fact, the SARS-CoV-2 proteome exhibits significant levels of structural order, with only the nucleocapsid (N) structural protein and two of the nonstructural proteins being highly disordered. The spike (S) protein of SARS-CoV-2 exhibits significant levels of structural order, yet its predicted percentage of intrinsic disorder is still higher than that of the spike protein of SARS-CoV. Noteworthy, however, even though IDPs/IDRs are not common in the SARS-CoV-2 proteome, the existing ones play major roles in the functioning and virulence of the virus and are thus promising drug targets for rational antiviral drug design. Presented here is a COVID-19 perspective on the intrinsically disordered proteins, summarizing recent results on the SARS-CoV-2 proteome disorder features, their physiological and pathological relevance, and their prominence as prospective drug target sites.

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Exothermic transitions in the heat capacity profiles of human cerebrospinal fluid

Cited by 7 publications

References 42 publications

Calorimetric Markers for Detection and Monitoring of Multiple Myeloma

Calorimetric Markers for Detection and Monitoring of Multiple Myeloma

Red Blood Cells’ Thermodynamic Behavior in Neurodegenerative Pathologies and Aging

Intrinsically Disordered Proteins: Perspective on COVID-19 Infection and Drug Discovery

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