Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
9.9
5.1
Journals
Cells
Special Issues
Proteostasis in Aging and Disease
share announcement

Proteostasis in Aging and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 17873

Special Issue Editor

Prof. Jari E. Koistinaho

E-Mail Website
Guest Editor
A.I. Virtanen Institute for Molecular Sciences, Laboratory of Molecular Brain Research, University of Eastern Finland, FI-70211 Kuopio, Finland
Interests: models of acute neurodegeneration (stroke, spinal cord injury) and chronic neurodegeneration (Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis); induced pluripotent stem cells in neurodegeneration; identification of drug molecules as a potentially therapeutic agents for brain diseases

Special Issue Information

Dear Colleagues,

Protein homeostasis, currently referred to as proteostasis, is a complex network of protein biogenesis, degradation, as well as their structural and functional maintenance within a cell or tissue. Proper proteostasis is essential for the preservation of the correct cellular proteome, virtually determining all its tasks in a tissue.

The role of proteostasis is continuously gaining increased recognition as an important factor contributing to human aging and disease, particularly to neurodegeneration. The capacity of cells to maintain proteostasis suffers from a decay upon aging, causing the vulnerability of an organism to the intrinsic and extrinsic stressors and resulting in pathology. In many neurodegenerative diseases where aging poses a major risk factor, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases, disturbed proteostasis is evident.

In this Special Issue, we aim to summarize the current knowledge of this important field and to give the possibility of sharing novel data on the multiple aspects of proteostasis in aging and disease.

We invite experts to contribute with research papers and critical reviews on the current state-of-the-art, including but not limited to proteostatic pathways for adaptation to cellular stress, protein misfolding, and clearance in diseases, and emerging therapeutic approaches for intervention in diseases of proteostasis.

Prof. Jari E. Koistinaho
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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

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

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

12 pages, 1126 KiB  
Article
Evaluating Serum Heat Shock Protein Levels as Novel Biomarkers for Atrial Fibrillation
by Denise M. S. van Marion, Eva A. H. Lanters, Kennedy S. Ramos, Jin Li, Marit Wiersma, Luciënne Baks-te Bulte, Agnes J. Q. M. Muskens, Eric Boersma, Natasja M. S. de Groot and Bianca J. J. M. Brundel
Cells 2020, 9(9), 2105; https://doi.org/10.3390/cells9092105 - 16 Sep 2020
Cited by 19 | Viewed by 3180
Abstract
Background: Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. [...] Read more.
Background: Staging of atrial fibrillation (AF) is essential to understanding disease progression and the accompanied increase in therapy failure. Blood-based heat shock protein (HSP) levels may enable staging of AF and the identification of patients with higher risk for AF recurrence after treatment. Objective: This study evaluates the relationship between serum HSP levels, presence of AF, AF stage and AF recurrence following electrocardioversion (ECV) or pulmonary vein isolation (PVI). Methods: To determine HSP27, HSP70, cardiovascular (cv)HSP and HSP60 levels, serum samples were collected from control patients without AF and patients with paroxysmal atrial fibrillation (PAF), persistent (PeAF) and longstanding persistent (LSPeAF) AF, presenting for ECV or PVI, prior to intervention and at 3-, 6- and 12-months post-PVI. Results: The study population (n = 297) consisted of 98 control and 199 AF patients admitted for ECV (n = 98) or PVI (n = 101). HSP27, HSP70, cvHSP and HSP60 serum levels did not differ between patients without or with PAF, PeAF or LSPeAF. Additionally, baseline HSP levels did not correlate with AF recurrence after ECV or PVI. However, in AF patients with AF recurrence, HSP27 levels were significantly elevated post-PVI relative to baseline, compared to patients without recurrence. Conclusions: No association was observed between baseline HSP levels and the presence of AF, AF stage or AF recurrence. However, HSP27 levels were increased in serum samples of patients with AF recurrence within one year after PVI, suggesting that HSP27 levels may predict recurrence of AF after ablative therapy. Full article
(This article belongs to the Special Issue Proteostasis in Aging and Disease)
►▼ Show Figures

Figure 1

22 pages, 5809 KiB  
Article
CUL4-DDB1-CRBN E3 Ubiquitin Ligase Regulates Proteostasis of ClC-2 Chloride Channels: Implication for Aldosteronism and Leukodystrophy
by Ssu-Ju Fu, Meng-Chun Hu, Yi-Jheng Peng, Hsin-Yu Fang, Cheng-Tsung Hsiao, Tsung-Yu Chen, Chung-Jiuan Jeng and Chih-Yung Tang
Cells 2020, 9(6), 1332; https://doi.org/10.3390/cells9061332 - 26 May 2020
Cited by 14 | Viewed by 4324
Abstract
Voltage-gated ClC-2 channels are essential for chloride homeostasis. Complete knockout of mouse ClC-2 leads to testicular degeneration and neuronal myelin vacuolation. Gain-of-function and loss-of-function mutations in the ClC-2-encoding human CLCN2 gene are linked to the genetic diseases aldosteronism and leukodystrophy, respectively. The protein [...] Read more.
Voltage-gated ClC-2 channels are essential for chloride homeostasis. Complete knockout of mouse ClC-2 leads to testicular degeneration and neuronal myelin vacuolation. Gain-of-function and loss-of-function mutations in the ClC-2-encoding human CLCN2 gene are linked to the genetic diseases aldosteronism and leukodystrophy, respectively. The protein homeostasis (proteostasis) mechanism of ClC-2 is currently unclear. Here, we aimed to identify the molecular mechanism of endoplasmic reticulum-associated degradation of ClC-2, and to explore the pathophysiological significance of disease-associated anomalous ClC-2 proteostasis. In both heterologous expression system and native neuronal and testicular cells, ClC-2 is subject to significant regulation by cullin-RING E3 ligase-mediated polyubiquitination and proteasomal degradation. The cullin 4 (CUL4)-damage-specific DNA binding protein 1 (DDB1)-cereblon (CRBN) E3 ubiquitin ligase co-exists in the same complex with and promotes the degradation of ClC-2 channels. The CRBN-targeting immunomodulatory drug lenalidomide and the cullin E3 ligase inhibitor MLN4924 promotes and attenuates, respectively, proteasomal degradation of ClC-2. Analyses of disease-related ClC-2 mutants reveal that aldosteronism and leukodystrophy are associated with opposite alterations in ClC-2 proteostasis. Modifying CUL4 E3 ligase activity with lenalidomide and MLN4924 ameliorates disease-associated ClC-2 proteostasis abnormality. Our results highlight the significant role and therapeutic potential of CUL4 E3 ubiquitin ligase in regulating ClC-2 proteostasis. Full article
(This article belongs to the Special Issue Proteostasis in Aging and Disease)
►▼ Show Figures

Figure 1

21 pages, 5520 KiB  
Article
The Co-Chaperone HspBP1 Is a Novel Component of Stress Granules that Regulates Their Formation
by Hicham Mahboubi, Ossama Moujaber, Mohamed Kodiha and Ursula Stochaj
Cells 2020, 9(4), 825; https://doi.org/10.3390/cells9040825 - 29 Mar 2020
Cited by 10 | Viewed by 4332
Abstract
The co-chaperone HspBP1 interacts with members of the hsp70 family, but also provides chaperone-independent functions. We report here novel biological properties of HspBP1 that are relevant to the formation of cytoplasmic stress granules (SGs). SG assembly is a conserved reaction to environmental or [...] Read more.
The co-chaperone HspBP1 interacts with members of the hsp70 family, but also provides chaperone-independent functions. We report here novel biological properties of HspBP1 that are relevant to the formation of cytoplasmic stress granules (SGs). SG assembly is a conserved reaction to environmental or pathological insults and part of the cellular stress response. Our study reveals that HspBP1 (1) is an integral SG constituent, and (2) a regulator of SG assembly. Oxidative stress relocates HspBP1 to SGs, where it co-localizes with granule marker proteins and polyA-RNA. Mass spectrometry and co-immunoprecipitation identified novel HspBP1-binding partners that are critical for SG biology. Specifically, HspBP1 associates with the SG proteins G3BP1, HuR and TIA-1/TIAR. HspBP1 also interacts with polyA-RNA in vivo and binds directly RNA homopolymers in vitro. Multiple lines of evidence and single-granule analyses demonstrate that HspBP1 is crucial for SG biogenesis. Thus, HspBP1 knockdown interferes with stress-induced SG assembly. By contrast, HspBP1 overexpression promotes SG formation in the absence of stress. Notably, the hsp70-binding domains of HspBP1 regulate SG production in unstressed cells. Taken together, we identified novel HspBP1 activities that control SG formation. These features expand HspBP1’s role in the cellular stress response and provide new mechanistic insights into SG biogenesis. Full article
(This article belongs to the Special Issue Proteostasis in Aging and Disease)
►▼ Show Figures

Figure 1

Review

Jump to: Research

23 pages, 973 KiB  
Review
Proteostasis Disturbances and Inflammation in Neurodegenerative Diseases
by Tuuli-Maria Sonninen, Gundars Goldsteins, Nihay Laham-Karam, Jari Koistinaho and Šárka Lehtonen
Cells 2020, 9(10), 2183; https://doi.org/10.3390/cells9102183 - 28 Sep 2020
Cited by 33 | Viewed by 5623
Abstract
Protein homeostasis (proteostasis) disturbances and inflammation are evident in normal aging and some age-related neurodegenerative diseases. While the proteostasis network maintains the integrity of intracellular and extracellular functional proteins, inflammation is a biological response to harmful stimuli. Cellular stress conditions can cause protein [...] Read more.
Protein homeostasis (proteostasis) disturbances and inflammation are evident in normal aging and some age-related neurodegenerative diseases. While the proteostasis network maintains the integrity of intracellular and extracellular functional proteins, inflammation is a biological response to harmful stimuli. Cellular stress conditions can cause protein damage, thus exacerbating protein misfolding and leading to an eventual overload of the degradation system. The regulation of proteostasis network is particularly important in postmitotic neurons due to their limited regenerative capacity. Therefore, maintaining balanced protein synthesis, handling unfolding, refolding, and degrading misfolded proteins are essential to preserve all cellular functions in the central nervous sysytem. Failing proteostasis may trigger inflammatory responses in glial cells, and the consequent release of inflammatory mediators may lead to disturbances in proteostasis. Here, we review the mechanisms of proteostasis and inflammatory response, emphasizing their role in the pathological hallmarks of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Furthermore, we discuss the interplay between proteostatic stress and excessive immune response that activates inflammation and leads to dysfunctional proteostasis. Full article
(This article belongs to the Special Issue Proteostasis in Aging and Disease)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop