Submit to Biomolecules Review for Biomolecules Propose a Special Issue

Journal Browser

► Journal Browser

Osmolyte System and Neurodegeneration: From Physiology to Therapeutics

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (1 March 2020) | Viewed by 22957

Share This Special Issue

Special Issue Editors

Dr. Safikur Rahman

E-Mail
Guest Editor

International Research Professor School of Medical Biotechnology, Yeungnam University, Gyeongsan, Korea
Interests: protein folding/unfolding; protein stabilization; osmolytes; protein denturation

Dr. Laishram Rajendrakumar Singh

E-Mail
Guest Editor

Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India
Interests: protein folding and stability and aggregation under macromolecular crowded conditions; role of osmolytes in protein folding; aggregation and amyloidosis; the hallmark of neurodegeneration; homocystinuria and role of homocysteine in neurodegeneration

Dr. Tanveer Ali Dar

E-Mail
Guest Editor

Clinical Biochemistry, University of Kashmir, Hazratbal Srinagar-190006, Jammu & Kashmir, India
Interests: regulation of folding; stability and functional activity of proteins by chemical chaperones/osmolytes; modulation/inhibition of aggregation/fibrillation of proteins by chemical chaperones/osmolytes

Special Issue Information

Dear Colleagues,

It is well known that protein aggregation or amyloid formation is one common hallmark of a large number of human diseases associated with brain cells because of the relatively poorly developed protein quality control (PQC) system. Much endeavor has been made toward the use of proteostatic modulators and identifying specific chaperones interacting with malfolded oligomerizing proteins. Neural-specific chaperones, proSAAS and 7B2 have also been identified. It is now believed that the osmolytes or chemical chaperones system is an important component of the PQC. These osmolytes are nontoxic, produced in large quantities under stress conditions, and induce folding of almost all of the unstable and nascent polypeptides as compared to molecular chaperones that require substrate specific folding. Various osmolytes have been demonstrated to have the ability to suppress protein aggregation or inhibit protein amyloid formation. Eventually, studies have already unveiled that osmolytes could be effective agents for Alzheimer’s disease, Parkinson disease, Poly-glutamine diseases, Huntington’s disease, amyotrophic lateral sclerosis, prion diseases, etc. Therefore, newer insights on how osmolytes reduce disease pathologies and chaperone proper folding of amyloidogenic protein oligomers are required. Osmolytes are also involved in the physiology of neuronal cells. Indeed, brain cells are housed with several osmolytic molecules, which include taurine, glutamate, myo-inositol, glutamine, creatine, and choline-containing compounds. Recently, it has been identified that N-acetylaspartate is also one important osmoprotectant in neuronal cells. In addition to their involvement in PQC, some of the osmoprotectants are anti-oxidants and also involved in important biological processes. Taurine and glutamate are also important neurotransmitters in the brain. Interestingly, osmolytes like Trimethylamine N-oxide have been shown to be neurotoxic and other osmolytes—for instance, betaine—could inhibit acetylcholine esterase. Further explorations are still required to exactly unveil their involvement in basic physiology, and also in neuro-modulation, synaptic plasticity, etc. Therefore, it is really important to make a comprehensively dedicated thematic issue that contains the role of osmolytes from the physiology of neuronal function to involvement in different disease etiologies or therapeutic potentials.

The purpose of this Special Issue of Biomolecules is to shed light on the latest outstanding discoveries pertinent in a wide spectrum of neuroscience by covering different aspects of the role of osmolytes on the nervous system to dementia, including synaptic plasticity, synaptic dysfunction, and on the inhibitory potentials of various candidate amyloidogenic proteins. Contributions are invited in the form of original research articles, reviews (mini and full length), case study, methods, hypothesis/theory, opinions and letters, commentary, etc.

Dr. Safikur Rahman
Dr. Laishram Rajendrakumar Singh
Dr. Tanveer Ali Dar
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly 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.

Keywords

osmolytes
chemical chaperons
neurodegeneration
protein misfolding

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

10 pages, 1391 KiB

Open AccessArticle

Myo-Inositol Transporter SLC5A3 Associates with Degenerative Changes and Inflammation in Sporadic Inclusion Body Myositis

by Boel De Paepe, Caroline Merckx, Jana Jarošová, Miryam Cannizzaro and Jan L. De Bleecker

Biomolecules 2020, 10(4), 521; https://doi.org/10.3390/biom10040521 - 30 Mar 2020

Cited by 13 | Viewed by 2979

Abstract

Myo-inositol exerts many cellular functions, which include osmo-protection, membrane functioning, and secondary messaging. Its Na⁺/myo-inositol co-transporter SLC5A3 is expressed in muscle tissue and further accumulates in myositis. In this study we focused on the peculiar subgroup of sporadic inclusion body myositis (IBM), in which auto-inflammatory responses and degenerative changes co-exist. A cohort of nine patients was selected with clinically confirmed IBM, in which SLC5A3 protein was immune-localized to the different tissue constituents using immunofluorescence, and expression levels were evaluated using Western blotting. In normal muscle tissue, SLC5A3 expression was restricted to blood vessels and occasional low levels on muscle fiber membranes. In IBM tissues, SLC5A3 staining was markedly increased, with discontinuous staining of the muscle fiber membranes, and accumulation of SLC5A3 near inclusions and on the rims of vacuoles. A subset of muscle-infiltrating auto-aggressive immune cells was SLC5A3 positive, of which most were T-cells and M1 lineage macrophages. We conclude that SLC5A3 is overexpressed in IBM muscle, where it associates with protein aggregation and inflammatory infiltration. Based on our results, functional studies could be initiated to explore the possibilities of therapeutic osmolyte pathway intervention for preventing protein aggregation in muscle cells. Full article

(This article belongs to the Special Issue Osmolyte System and Neurodegeneration: From Physiology to Therapeutics)

► Show Figures

Figure 1

10 pages, 2223 KiB

Open AccessArticle

N-Acetylaspartate Is an Important Brain Osmolyte

by Marina Warepam, Khurshid Ahmad, Safikur Rahman, Hamidur Rahaman, Kritika Kumari and Laishram Rajendrakumar Singh

Biomolecules 2020, 10(2), 286; https://doi.org/10.3390/biom10020286 - 12 Feb 2020

Cited by 12 | Viewed by 2589

Abstract

Most of the human diseases related to various proteopathies are confined to the brain, which leads to the development of various forms of neurological disorders. The human brain consists of several osmolytic compounds, such as N-Acetylaspartate (NAA), myo-inositol (mI), glutamate (Glu), glutamine (Gln), creatine (Cr), and choline-containing compounds (Cho). Among these osmolytes, the level of NAA drastically decreases under neurological conditions, and, hence, NAA is considered to be one of the most widely accepted neuronal biomarkers in several human brain disorders. To date, no data are available regarding the effect of NAA on protein stability, and, therefore, the possible effect of NAA under proteopathic conditions has not been fully uncovered. To gain an insight into the effect of NAA on protein stability, thermal denaturation and structural measurements were carried out using two model proteins at different pH values. The results indicate that NAA increases the protein stability with an enhancement of structure formation. We also observed that the stabilizing ability of NAA decreases in a pH-dependent manner. Our study indicates that NAA is an efficient protein stabilizer at a physiological pH. Full article

(This article belongs to the Special Issue Osmolyte System and Neurodegeneration: From Physiology to Therapeutics)

► Show Figures

Figure 1

13 pages, 2044 KiB

Open AccessArticle

Unraveling Binding Mechanism of Alzheimer’s Drug Rivastigmine Tartrate with Human Transferrin: Molecular Docking and Multi-Spectroscopic Approach towards Neurodegenerative Diseases

by Anas Shamsi, Taj Mohammad, Mohd Shahnawaz Khan, Moyad Shahwan, Fohad Mabood Husain, Md. Tabish Rehman, Md. Imtaiyaz Hassan, Faizan Ahmad and Asimul Islam

Biomolecules 2019, 9(9), 495; https://doi.org/10.3390/biom9090495 - 17 Sep 2019

Cited by 47 | Viewed by 3561

Abstract

Studying drug–protein interactions has gained significant attention lately, and this is because the majority of drugs interact with proteins, thereby altering their structure and, moreover, their functionality. Rivastigmine tartrate (RT) is a drug that is in use for mild to moderate Alzheimer therapy. This study was targeted to characterize the interaction between human transferrin (hTf) and RT by employing spectroscopy, isothermal titration calorimetry (ITC), and molecular docking studies. Experimental results of fluorescence quenching of hTf induced by RT implied the formation of a static complex between hTf and RT. Further elucidation of the observed fluorescence data retorting Stern–Volmer and modified Stern–Volmer resulted in binding constants for hTf–RT complex of the order 10⁴ M⁻¹ over the studied temperatures. Thermodynamic parameters of hTf–RT interaction were elucidated further by employing these obtained binding constant values. It was quite evident from obtained thermodynamic attributes that RT spontaneously binds to hTf with a postulated existence of hydrogen bonding or Van der Waals forces. Further, Circular dichroism spectroscopy (CD) also confirmed RT–hTf complex formation owing to upward movement of CD spectra in the presence of RT. ITC profiles advocated the existence of reaction to be spontaneous. Moreover, molecular docking further revealed that the important residues play a pivotal role in RT–hTf interaction. The findings of this study can be of a significant benefit to the drug-designing industry in this disease-prone era. Full article

(This article belongs to the Special Issue Osmolyte System and Neurodegeneration: From Physiology to Therapeutics)

► Show Figures

Graphical abstract

Review

Jump to: Research

22 pages, 2811 KiB

Open AccessReview

Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases

by Mujtaba Aamir Bhat, Khurshid Ahmad, Mohd Sajjad Ahmad Khan, Mudasir Ahmad Bhat, Ahmad Almatroudi, Safikur Rahman and Arif Tasleem Jan

Biomolecules 2020, 10(6), 863; https://doi.org/10.3390/biom10060863 - 5 Jun 2020

Cited by 17 | Viewed by 4362

Abstract

Neurodegenerative diseases (NDs) are characterized by the accumulation of misfolded proteins. The hallmarks of protein aggregation in NDs proceed with impairment in the mitochondrial function, besides causing an enhancement in endoplasmic reticulum (ER) stress, neuroinflammation and synaptic loss. As accumulation of misfolded proteins hampers normal neuronal functions, it triggers ER stress, which leads to the activation of downstream effectors formulating events along the signaling cascade—referred to as unfolded protein response (UPRER) —thereby controlling cellular gene expression. The absence of disease-modifying therapeutic targets in different NDs, and the exponential increase in the number of cases, makes it critical to explore new approaches to treating these devastating diseases. In one such approach, osmolytes (low molecular weight substances), such as taurine have been found to promote protein folding under stress conditions, thereby averting aggregation of the misfolded proteins. Maintaining the structural integrity of the protein, taurine-mediated resumption of protein folding prompts a shift in folding homeostasis more towards functionality than towards aggregation and degradation. Together, taurine enacts protection in NDs by causing misfolded proteins to refold, so as to regain their stability and functionality. The present study provides recent and useful insights into understanding the progression of NDs, besides summarizing the genetics of NDs in correlation with mitochondrial dysfunction, ER stress, neuroinflammation and synaptic loss. It also highlights the structural and functional aspects of taurine in imparting protection against the aggregation/misfolding of proteins, thereby shifting the focus more towards the development of effective therapeutic modules that could avert the development of NDs. Full article

(This article belongs to the Special Issue Osmolyte System and Neurodegeneration: From Physiology to Therapeutics)

► Show Figures

Figure 1

11 pages, 1477 KiB

Open AccessReview

Osmolytes: A Possible Therapeutic Molecule for Ameliorating the Neurodegeneration Caused by Protein Misfolding and Aggregation

by Neetu Kushwah, Vishal Jain and Dhananjay Yadav

Biomolecules 2020, 10(1), 132; https://doi.org/10.3390/biom10010132 - 13 Jan 2020

Cited by 31 | Viewed by 8614

Abstract

Most of the neurological disorders in the brain are caused by the abnormal buildup of misfolded or aggregated proteins. Osmolytes are low molecular weight organic molecules usually built up in tissues at a quite high amount during stress or any pathological condition. These molecules help in providing stability to the aggregated proteins and protect these proteins from misfolding. Alzheimer’s disease (AD) is the uttermost universal neurological disorder that can be described by the deposition of neurofibrillary tangles, aggregated/misfolded protein produced by the amyloid β-protein (Aβ). Osmolytes provide stability to the folded, functional form of a protein and alter the folding balance away from aggregation and/or degradation of the protein. Moreover, they are identified as chemical chaperones. Brain osmolytes enhance the pace of Aβ aggregation, combine with the nearby water molecules more promptly, and avert the aggregation/misfolding of proteins by providing stability to them. Therefore, osmolytes can be employed as therapeutic targets and may assist in potential drug design for many neurodegenerative and other diseases. Full article

(This article belongs to the Special Issue Osmolyte System and Neurodegeneration: From Physiology to Therapeutics)

► Show Figures