Transglutaminase inhibition: possible therapeutic mechanisms to protect cells from death in neurological disorders
Published on: 25th July, 2017
OCLC Number/Unique Identifier: 7317595344
Transglutaminases are a family of Ca2+-dependent enzymes which catalyze post-translational modifications of proteins. The main activity of these enzymes is the cross-linking of glutaminyl residues of a protein/peptide substrate to lysyl residues of a protein/peptide co-substrate. In addition to lysyl residues, other second nucleophilic co-substrates may include monoamines or polyamines (to form mono-or bi-substituted/crosslinked adducts) or -OH groups (to form ester linkages). In absence of co-substrates, the nucleophile may be water, resulting in the net deamidation of the glutaminyl residue. Transglutaminase activity has been suggested to be involved in molecular mechanisms responsible for both physiological and pathological processes. In particular, transglutaminase activity has been shown to be responsible for human autoimmune diseases, and Celiac Disease is just one of them. Interestingly, neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, supranuclear palsy, Huntington’s disease and other polyglutamine diseases, are characterized in part by aberrant cerebral transglutaminase activity and by increased cross-linked proteins in affected brains. Here we describe the possible molecular mechanisms by which these enzymes could be responsible for such diseases and the possible use of transglutaminase inhibitors for patients with diseases characterized by aberrant transglutaminase activity.
Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species
Published on: 4th November, 2019
OCLC Number/Unique Identifier: 8302209826
The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed.
Role of neuron specific enolase as a biomarker in Parkinson’s disease
Published on: 6th July, 2021
OCLC Number/Unique Identifier: 9137583301
Parkinson’s disease (PD) is thought to be the most common neurodegenerative disease with movement disorder. The key motor symptoms are rigidity, tremor, akinesis/hypokinesia/bradykinesia, and postural instability. However, in our day-to-day clinical practice we tend to see several other symptoms which may be motor or non-motor. Non-motor symptoms (NMS) are quite common and debilitating. The pathological hallmarks of PD are loss of dopaminergic neurons in the substantia nigra pars compacta (SNPc) and accumulation of unfolded or misfolded alpha-synuclein. Diagnosis of PD is difficult in the pre-motor stage. Late diagnosis renders a substantial loss of dopaminergic neurons in SNPc and spread of disease in other parts of the brain. This may manifest as either full blown symptoms requiring multiple medications or may even lead to life threatening condition due to lack of early diagnostic tools and techniques. Biomarkers are required to diagnose PD at a very early stage when prevention is possible. Hence, we see a lot of interest among researchers involved in finding a biomarker specific to the disease. Biomarkers may be clinical, image based, genetic, and biochemical. Cerebrospinal fluid (CSF) and serum markers which may correlate with disease pathophysiology are of great significance. One such molecule which recently gained a lot of attention is neuron-specific enolase (NSE). The main aim of this paper is to highlight the role of NSE in predicting neurodegeneration and neuroinflammation ultimately reflecting damage of brain cells in PD.
A Water-soluble Form of Dihydroquercetin Reduces LPS-induced Astrogliosis, Vascular Remodeling, and mRNA VEGF-A Levels in the Substantia Nigra of Aged Rats
Published on: 16th February, 2024
Background: The age-dependent sporadic form of PD is characterized by the degeneration of dopaminergic (DA) neurons in the Substantia Nigra (SN), gliosis, and vascular changes. Vascular changes may contribute to the onset of the disease and exacerbate the neurodegenerative process, as some vascular changes occur before the onset of neuronal loss. To demonstrate the anti-neuroinflammatory efficacy of a new compound, a water-soluble form of dihydroquercetin (DHQ-WF), we studied the structural changes of microcirculatory vasculature, astroglial GFAP, and vascular endothelial growth factor –A (VEGF-A) mRNA expression in the SN of young and old rats after unilateral nigral treatment by lipopolysaccharide (LPS) and oral administration of DHQ-WF.Materials and methods: The experiments were performed on 18 young (8 weeks - 10 weeks old; 250 g - 320 g) and 18 old (18 months - 19 months old; 390 g - 450 g) male Vistar rats. Young and adult rats from the experimental groups were stereotactically injected with 2 μL LPS solution (LPS from Escherichia coli; 0,01 μL/mL) into one side of the SN. Control young and old rats were similarly injected with 2 μL sterile saline. Half of the animals in both the control and experimental groups (6 animals in each group) received a 2 ml solution containing DHQ-WF at a concentration of 3 mg/ml orally every day. After 8 weeks, brains were harvested and serial cryostat sections were prepared for histochemical (FITC-labeled tomato lectin), immunohistochemical (anti-GFAP Antibody, Cy3 Conjugate) staining, and real-time PCR (mRNA VEGF-A).Results: Eight weeks after LPS injection into the SN, a significant excess of areas occupied by cell bodies and processes of astroglial cells, the density of microcirculatory vessels, and mRNA VEGF-A expression was observed in old animals compared to control old animals and young LPS-treated rats. Oral administration of DHQ-WF to LPS-treated rats resulted in a significant reduction of these parameters in old animals.Conclusion: Injection of LPS into rat SN induces neuroinflammation and vascular angiogenesis, maximally expressed in old animals. Administration of DHQ-WF for 8 weeks significantly reduces these LPS-induced changes. DHQ-WF may be an effective treatment for reducing the effects of neuroinflammation in the aging brain.
Search by University/Institution
Enter your University/Institution to find colleagues at HSPI.
Ensuring author's satisfaction with
- Friendly and hassle-free publication process
- Less production time of articles
- Constructive peer-review
- Enhancing journal reputation
- Regular feedback system
- Quick response to authors' queries
Most Viewed Keywords
- Goldenhar syndrome
- Vitamin D deficiency
- Occluded coronary artery
- DNA
- Magnetic resonance imaging
- Down syndrome
- Medico legal death investigation system
- Extracorporeal shock wave
- Lighvan cheese
- Laser-induced magnetization
- Anomalies of coronary artery origin
- Hemiscorpius lepturus
- Choriocarcinoma
- Pulmonary mucormycosis
- Obesity
- Blood pressure
- African palm
- Extra blood purification therapies
- Gender change surgery
- Indigenous knowledge
Search Articles by Country
Get all latest articles in all Heighten Science Publications Inc journals by country.
Testmonials
Thank you and your company for effective support of authors which are very much dependable on the funds gambling for science in the different countries of our huge and unpredictable world. We are doing our work and should rely on a teams like Galley Proof-HSPC. Great success to all of you for the 2019th! Be well all the year long.
Russia
Victor V Apollonov
“It was a delightful experience publishing my manuscript with the Clinical Journal of Obstetrics and Gynecology. They offered me lots of opportunities I never had from most publishing houses and their prompt services are greatly appreciated.”
Asafo Jones
This is to specify that I have had an extensive and detailed interaction with the Editorial team of Annals of Clinical Gastroenterology and Hepatology, USA, lasting over a significant period of time. My interaction has been extremely pleasant, especially with Ms Allie Smith, as I find the communication quite inspiring and crystal clear. The attitude of aforesaid individuals is quite helpful and guiding in pertinent instances. It has been a commemorative journey so far working with the Journal and I hope that the symbiosis will continue, evolve and flourish in the forthcoming years. I wish the journal, related personnel and aforementioned individuals a fruitful, successful run.
New Delhi, India
Anubha Bajaj
Thank you very much for your support and encouragement. I am truly impressed by your tolerance and support. Thank you very much
Diaverum: PADC, Jeddah, Saudi Arabia
Nasrulla Abutaleb
We really appreciate and thanks the full waiver you provide for our article. We happy to publish our paper in your journal. Thank you very much for your good support and services.
Ali Abusafia
I am very much pleased with the fast track publication by your reputed journal's editorial team. It is really helpful for researchers like me from developing nations. I strongly recommend your journal for publication.
Badri Kumar Gupta
My candid opinion is that the service you render is second to none. My favourite part is the prompt response to issue, really i value that.
Abiodun Akanbi Adeogun
Publishing with the International Journal of Clinical and Experimental Ophthalmology was a rewarding experience as review process was thorough and brisk. Their visibility online is second to none as their published articles appear in all search engines. I will encourage researchers to publish with them.
Elizabeth Awoyesuku
I, Muhammad Sarwar Khan, am serving as Editor on Archives of Biotechnology and Biomedicine (ABB). I submitted an editorial titled, 'Edible vaccines to combat Infectious Bursal Disease of poultry' for publication in ABB. After submitting the manuscript; the services rendered by the management and technical personnel to handle and process the manuscript were marvelous. Plagiarism report was shared with me with complements before reviewers' comments, All steps including article processing and service charges were well taken care of keeping in view the author's interest/preference. All together, it was an encouraging and wonderful experience working with ABB personnel.
University of Agriculture, Pakistan
Muhammad Sarwar Khan
The Journal Clinical Nephrology provides a good opportunity for readers to stay updated in the field of clinical nephrology. Additionally - it provides a good opportunity for authors to publish their work. 1. Publication of the accepted manuscripts is sufficiently rapid. 2. The trust factor between the journal and me, as an author, is very important and well preserved. 3. Peer review process very rapid and effective.
Assaf Harofeh Medical Center, Israel
Leonid Feldman
