Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Benefits of Publishing in a Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 28572

Share This Special Issue

Special Issue Editors

Prof. Dr. Carlos Gutierrez-Merino

E-Mail Website
Guest Editor

Professor of Biochemistry and Molecular Biology, Department of Biochemistry and Molecular Biology, Faculty of Sciences, and Institute of Molecular Pathology Biomarkers, University of Extremadura, Badajoz, Spain
Interests: tissue degeneration; biomaker; amyloid β-calmodulin
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Ana M. Mata

E-Mail
Co-Guest Editor

Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura and Instituto de Biomarcadores de Patologías Moleculares, Universidad de Extremadura, 06006 Badajoz, Spain

Special Issue Information

Dear Colleagues,

Mammalian tissue degeneration plays a major role either at the onset or in the early stages of many chronic diseases and insults to human health. A common feature of these threats to human health is that they initially develop slowly until tissue degeneration reaches an irreversible critical point. This critical point is currently associated with the activation of the proteases inducing cell death by apoptosis, necrosis or lysosomal dysfunction (including autophagocytosis).

Studies of the molecular mechanisms underlying the biological dysregulation at the early and yet reversible stage of mammalian tissue degeneration are providing relevant clues to the most relevant molecular events triggering entry into the irreversible stage. The current knowledge points out that this early stage is a complex and multifactorial process induced by endogenous factors or exposure to drugs or environmental toxins that in most cases produce tissue inflammation, sustained cellular oxidative stress, and bioenergetic and cellular signaling dysregulation. Thus, there is a need to evaluate the relative contribution of different putative molecular mechanisms of dysregulation in each particular case, as well as the temporal sequence of molecular events that can lead to entry into the irreversible stage of tissue degeneration. Therefore, research on these molecular mechanisms is providing the most relevant biomarkers and biological targets for early diagnosis of the disease and/or for the design of rational therapeutic approaches to slow down or attenuate the severity of the health damage.

It is the aim of this Special Issue to focus on recent advances in the molecular mechanisms of biological dysregulation in the early and yet reversible stage of mammalian tissue degeneration.

Prof. Dr. Carlos Gutierrez-Merino
Prof. Dr. Ana M. Mata
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 193 KiB

Open AccessEditorial

Special Issue “Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration”

by Carlos Gutierrez-Merino and Ana M. Mata

Int. J. Mol. Sci. 2022, 23(12), 6358; https://doi.org/10.3390/ijms23126358 - 7 Jun 2022

Viewed by 1339

Abstract

Tissue degeneration is an event shared by many, if not all, age-related pathologies [...] Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

Research

Jump to: Editorial, Review

16 pages, 54149 KiB

Open AccessArticle

Myocardial Accumulations of Reg3A, Reg3γ and Oncostatin M Are Associated with the Formation of Granulomata in Patients with Cardiac Sarcoidosis

by Praveen Gajawada, Ayse Cetinkaya, Susanne von Gerlach, Natalia Kubin, Heiko Burger, Michael Näbauer, Carola Grinninger, Andreas Rolf, Markus Schönburg, Yeong-Hoon Choi, Thomas Kubin and Manfred Richter

Int. J. Mol. Sci. 2021, 22(8), 4148; https://doi.org/10.3390/ijms22084148 - 16 Apr 2021

Cited by 9 | Viewed by 4083

Abstract

Cardiac sarcoidosis (CS) is a poorly understood disease and is characterized by the focal accumulation of immune cells, thus leading to the formation of granulomata (GL). To identify the developmental principles of fatal GL, fluorescence microscopy and Western blot analysis of CS and control patients is presented here. CS is visualized macroscopically by positron emission tomography (PET)/ computed tomography (CT). A battery of antibodies is used to determine structural, cell cycle and inflammatory markers. GL consist of CD68⁺, CD163⁺ and CD206⁺ macrophages surrounded by T-cells within fibrotic areas. Cell cycle markers such as phospho-histone H3, phospho-Aurora and Ki67 were moderately present; however, the phosphorylated ERM (ezrin, radixin and moesin) and Erk1/2 proteins, strong expression of the myosin motor protein and the macrophage transcription factor PU.1 indicate highly active GL. Mild apoptosis is consistent with PI3 kinase and Akt activation. Massive amounts of the IL-1R antagonist reflect a mild activation of stress and inflammatory pathways in GL. High levels of oncostatin M and the Reg3A and Reg3γ chemokines are in accordance with macrophage accumulation in areas of remodeling cardiomyocytes. We conclude that the formation of GL occurs mainly through chemoattraction and less by proliferation of macrophages. Furthermore, activation of the oncostatin/Reg3 axis might help at first to wall-off substances but might initiate the chronic development of heart failure. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

► Show Figures

Figure 1

19 pages, 6513 KiB

Open AccessArticle

Early Reactive A1 Astrocytes Induction by the Neurotoxin 3-Nitropropionic Acid in Rat Brain

by Carmen Lopez-Sanchez, Virginio Garcia-Martinez, Joana Poejo, Virginio Garcia-Lopez, Jairo Salazar and Carlos Gutierrez-Merino

Int. J. Mol. Sci. 2020, 21(10), 3609; https://doi.org/10.3390/ijms21103609 - 20 May 2020

Cited by 29 | Viewed by 4224

Abstract

3-Nitropropionic acid (NPA) administration to rodents produces degeneration of the striatum, accompanied by neurological disturbances that mimic Huntington’s disease (HD) motor neurological dysfunctions. It has been shown that inflammation mediates NPA-induced brain degeneration, and activated microglia secreting cytokines interleukin-1α (IL-1α) and tumor necrosis factor α (TNFα) can induce a specific type of reactive neurotoxic astrocytes, named A1, which have been detected in post-mortem brain samples of Huntington’s, Alzheimer’s, and Parkinson’s diseases. In this work we used an experimental model based on the intraperitoneal (i.p.) administration of NPA to adult Wistar rats at doses that can elicit extensive brain degeneration, and brain samples were taken before and after extensive brain damage monitored using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western blots and immunohistochemistry of brain slices show that i.p. NPA injections elicit significant increase in the expression levels of C3α subunit, a marker of generation of neurotoxic A1 astrocytes, and of cytokines IL-1α, TNFα, and C1q within the striatum, hippocampus, and cerebellum before the appearance of the HD-related neurological dysfunctions and neuronal death induced by NPA. Noteworthy, NPA administration primarily induces the generation of A1 astrocytes in the more recent phylogenetic area of the rat cerebellum. We conclude that the activation of complement C3 protein in the brain from Wistar rats is an early event in NPA-induced brain neurodegeneration. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

► Show Figures

Figure 1

13 pages, 1377 KiB

Open AccessArticle

Age-Induced Differential Changes in the Central and Colonic Human Circadian Oscillators

by Cristina Camello-Almaraz, Francisco E. Martin-Cano, Francisco J. Santos, Mª Teresa Espin, Juan Antonio Madrid, Maria J. Pozo and Pedro J. Camello

Int. J. Mol. Sci. 2020, 21(2), 674; https://doi.org/10.3390/ijms21020674 - 20 Jan 2020

Cited by 5 | Viewed by 3566

Abstract

Aging modifies not only multiple cellular and homeostatic systems, but also biological rhythms. The circadian system is driven by a central hypothalamic oscillator which entrains peripheral oscillators, in both cases underlain by circadian genes. Our aim was to characterize the effect of aging in the circadian expression of clock genes in the human colon. Ambulatory recordings of the circadian rhythms of skin wrist temperature, motor activity and the integrated variable TAP (temperature, activity and position) were dampened by aging, especially beyond 74 years of age. On the contrary, quantitative analysis of genes expression in the muscle layer of colonic explants during 24 h revealed that the circadian expression of Bmal1, Per1 and Clock genes, was larger beyond that age. In vitro experiments showed that aging induced a parallel increase in the myogenic contractility of the circular colonic muscle. This effect was not accompanied by enhancement of Ca²⁺ signals. In conclusion, we describe here for the first time the presence of a molecular oscillator in the human colon. Aging has a differential effect on the systemic circadian rhythms, that are impaired by aging, and the colonic oscillator, that is strengthened in parallel with the myogenic contractility. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

20 pages, 635 KiB

Open AccessReview

The Relevance of Amyloid β-Calmodulin Complexation in Neurons and Brain Degeneration in Alzheimer’s Disease

by Joana Poejo, Jairo Salazar, Ana M. Mata and Carlos Gutierrez-Merino

Int. J. Mol. Sci. 2021, 22(9), 4976; https://doi.org/10.3390/ijms22094976 - 7 May 2021

Cited by 19 | Viewed by 3122

Abstract

Intraneuronal amyloid β (Aβ) oligomer accumulation precedes the appearance of amyloid plaques or neurofibrillary tangles and is neurotoxic. In Alzheimer’s disease (AD)-affected brains, intraneuronal Aβ oligomers can derive from Aβ peptide production within the neuron and, also, from vicinal neurons or reactive glial cells. Calcium homeostasis dysregulation and neuronal excitability alterations are widely accepted to play a key role in Aβ neurotoxicity in AD. However, the identification of primary Aβ-target proteins, in which functional impairment initiating cytosolic calcium homeostasis dysregulation and the critical point of no return are still pending issues. The micromolar concentration of calmodulin (CaM) in neurons and its high affinity for neurotoxic Aβ peptides (dissociation constant ≈ 1 nM) highlight a novel function of CaM, i.e., the buffering of free Aβ concentrations in the low nanomolar range. In turn, the concentration of Aβ-CaM complexes within neurons will increase as a function of time after the induction of Aβ production, and free Aβ will rise sharply when accumulated Aβ exceeds all available CaM. Thus, Aβ-CaM complexation could also play a major role in neuronal calcium signaling mediated by calmodulin-binding proteins by Aβ; a point that has been overlooked until now. In this review, we address the implications of Aβ-CaM complexation in the formation of neurotoxic Aβ oligomers, in the alteration of intracellular calcium homeostasis induced by Aβ, and of dysregulation of the calcium-dependent neuronal activity and excitability induced by Aβ. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

10 pages, 443 KiB

Open AccessReview

Protein Biomarkers for the Diagnosis of Alzheimer’s Disease at Different Stages of Neurodegeneration

by Mar Pérez, Félix Hernández and Jesús Avila

Int. J. Mol. Sci. 2020, 21(18), 6749; https://doi.org/10.3390/ijms21186749 - 15 Sep 2020

Cited by 4 | Viewed by 3175

Abstract

Mainly obtained from familial Alzheimer’s disease patients’ data, we know that some features of the neurodegenerative start several years before the appearance of clinical symptoms. In this brief review, we comment on some molecular and cellular markers appearing at different stages of the disease, before or once the clinical symptoms are evident. These markers are present in biological fluids or could be identified by image techniques. The combined use of molecular and cellular markers will be of interest to determine the development of the different phases of the disease. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

► Show Figures

Figure 1

26 pages, 840 KiB

Open AccessReview

The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer′s Disease (AD)

by Barbara Mroczko, Magdalena Groblewska and Ala Litman-Zawadzka

Int. J. Mol. Sci. 2019, 20(19), 4661; https://doi.org/10.3390/ijms20194661 - 20 Sep 2019

Cited by 55 | Viewed by 8165

Abstract

Although the causative role of the accumulation of amyloid β 1–42 (Aβ42) deposits in the pathogenesis of Alzheimer′s disease (AD) has been under debate for many years, it is supposed that the toxicity soluble oligomers of Tau protein (TauOs) might be also the pathogenic factor acting on the initial stages of this disease. Therefore, we performed a thorough search for literature pertaining to our investigation via the MEDLINE/PubMed database. It was shown that soluble TauOs, especially granular forms, may be the most toxic form of this protein. Hyperphosphorylated TauOs can reduce the number of synapses by missorting into axonal compartments of neurons other than axon. Furthermore, soluble TauOs may be also responsible for seeding Tau pathology within AD brains, with probable link to AβOs toxicity. Additionally, the concentrations of TauOs in the cerebrospinal fluid (CSF) and plasma of AD patients were higher than in non-demented controls, and revealed a negative correlation with mini-mental state examination (MMSE) scores. It was postulated that adding the measurements of TauOs to the panel of CSF biomarkers could improve the diagnosis of AD. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration)

► Show Figures

Journal Menu

Journal Browser

Molecular and Cellular Mechanisms of Action of Markers of Tissue Degeneration

Share This Special Issue

Special Issue Editors

Special Issue Information

Benefits of Publishing in a Special Issue

Published Papers (7 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI