Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies

Discovery of diagnostic biomarkers for age-related neurodegenerative pathologies (NDDs) is essential for accurate diagnosis, following disease progression and drug development. Blood plasma and blood cells are important peripheral sources for NDDs’ biomarkers that, although present in lower concentr...

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Main Authors: Avgustina Danailova, Svetla Todinova, Lidia Gartcheva, Desislava Bogdanova, Elena Zlatareva, Nikolay Kalaydzhiev, Ivan Milanov, Sashka Krumova, Stefka G. Taneva
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/1/789
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author Avgustina Danailova
Svetla Todinova
Lidia Gartcheva
Desislava Bogdanova
Elena Zlatareva
Nikolay Kalaydzhiev
Ivan Milanov
Sashka Krumova
Stefka G. Taneva
author_facet Avgustina Danailova
Svetla Todinova
Lidia Gartcheva
Desislava Bogdanova
Elena Zlatareva
Nikolay Kalaydzhiev
Ivan Milanov
Sashka Krumova
Stefka G. Taneva
author_sort Avgustina Danailova
collection DOAJ
description Discovery of diagnostic biomarkers for age-related neurodegenerative pathologies (NDDs) is essential for accurate diagnosis, following disease progression and drug development. Blood plasma and blood cells are important peripheral sources for NDDs’ biomarkers that, although present in lower concentrations than in cerebrospinal fluid, would allow noninvasive diagnostics. To identify new biomarkers for Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), in this work we have evaluated the modifications in the thermodynamic behavior of blood plasma proteome exploring differential scanning calorimetry. The plasma thermodynamics reflected the complexity and heterogeneity of the two pathologies. The unfolding temperature of the most abundant plasma protein albumin and the weighted average center of the calorimetric profile appeared as the two thermodynamic signatures that reflected modifications of the plasma proteome, i.e., strong thermal stabilization of albumin and plasma proteins’ interaction network, related to both pathologies. Based on those two signatures, both PD and ALS patients were stratified in two sets, except several cases with thermodynamic parameters that strongly differed from those of the calorimetric sets. Along with modifications of the plasma thermodynamic behavior, we found altered globulin levels in all PD and ALS patients’ plasma (higher level of α- and β-globulin fractions and lower level of γ-globulin fraction than the respective reference values) employing capillary electrophoresis. The presented results reveal the potential of calorimetry to indirectly identify NDDs’ biomarkers in blood plasma.
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spelling doaj.art-4ef042598c474642991ce9b5c112173c2023-11-16T15:38:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-0124178910.3390/ijms24010789Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative PathologiesAvgustina Danailova0Svetla Todinova1Lidia Gartcheva2Desislava Bogdanova3Elena Zlatareva4Nikolay Kalaydzhiev5Ivan Milanov6Sashka Krumova7Stefka G. Taneva8Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str. 21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str. 21, 1113 Sofia, BulgariaNational Specialized Hospital for Active Treatment of Haematological Diseases, “Plovdivsko pole” Str. 6, 1756 Sofia, BulgariaUniversity Multiprofile Hospital for Active Treatment in Neurology and Psychiatry “St. Naum”, “Louben Roussev” Str. 1, 1113 Sofia, BulgariaUniversity Multiprofile Hospital for Active Treatment in Neurology and Psychiatry “St. Naum”, “Louben Roussev” Str. 1, 1113 Sofia, BulgariaUniversity Multiprofile Hospital for Active Treatment in Neurology and Psychiatry “St. Naum”, “Louben Roussev” Str. 1, 1113 Sofia, BulgariaUniversity Multiprofile Hospital for Active Treatment in Neurology and Psychiatry “St. Naum”, “Louben Roussev” Str. 1, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str. 21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str. 21, 1113 Sofia, BulgariaDiscovery of diagnostic biomarkers for age-related neurodegenerative pathologies (NDDs) is essential for accurate diagnosis, following disease progression and drug development. Blood plasma and blood cells are important peripheral sources for NDDs’ biomarkers that, although present in lower concentrations than in cerebrospinal fluid, would allow noninvasive diagnostics. To identify new biomarkers for Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), in this work we have evaluated the modifications in the thermodynamic behavior of blood plasma proteome exploring differential scanning calorimetry. The plasma thermodynamics reflected the complexity and heterogeneity of the two pathologies. The unfolding temperature of the most abundant plasma protein albumin and the weighted average center of the calorimetric profile appeared as the two thermodynamic signatures that reflected modifications of the plasma proteome, i.e., strong thermal stabilization of albumin and plasma proteins’ interaction network, related to both pathologies. Based on those two signatures, both PD and ALS patients were stratified in two sets, except several cases with thermodynamic parameters that strongly differed from those of the calorimetric sets. Along with modifications of the plasma thermodynamic behavior, we found altered globulin levels in all PD and ALS patients’ plasma (higher level of α- and β-globulin fractions and lower level of γ-globulin fraction than the respective reference values) employing capillary electrophoresis. The presented results reveal the potential of calorimetry to indirectly identify NDDs’ biomarkers in blood plasma.https://www.mdpi.com/1422-0067/24/1/789blood plasma biomarkersParkinson’s diseaseamyotrophic lateral sclerosisdifferential scanning calorimetrythermal transitionstransition temperature
spellingShingle Avgustina Danailova
Svetla Todinova
Lidia Gartcheva
Desislava Bogdanova
Elena Zlatareva
Nikolay Kalaydzhiev
Ivan Milanov
Sashka Krumova
Stefka G. Taneva
Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies
International Journal of Molecular Sciences
blood plasma biomarkers
Parkinson’s disease
amyotrophic lateral sclerosis
differential scanning calorimetry
thermal transitions
transition temperature
title Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies
title_full Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies
title_fullStr Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies
title_full_unstemmed Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies
title_short Thermodynamic Signatures of Blood Plasma Proteome in Neurodegenerative Pathologies
title_sort thermodynamic signatures of blood plasma proteome in neurodegenerative pathologies
topic blood plasma biomarkers
Parkinson’s disease
amyotrophic lateral sclerosis
differential scanning calorimetry
thermal transitions
transition temperature
url https://www.mdpi.com/1422-0067/24/1/789
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AT desislavabogdanova thermodynamicsignaturesofbloodplasmaproteomeinneurodegenerativepathologies
AT elenazlatareva thermodynamicsignaturesofbloodplasmaproteomeinneurodegenerativepathologies
AT nikolaykalaydzhiev thermodynamicsignaturesofbloodplasmaproteomeinneurodegenerativepathologies
AT ivanmilanov thermodynamicsignaturesofbloodplasmaproteomeinneurodegenerativepathologies
AT sashkakrumova thermodynamicsignaturesofbloodplasmaproteomeinneurodegenerativepathologies
AT stefkagtaneva thermodynamicsignaturesofbloodplasmaproteomeinneurodegenerativepathologies