scholarly journals The Role of S-Nitrosylation and S-Glutathionylation of Protein Disulphide Isomerase in Protein Misfolding and Neurodegeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
M. Halloran ◽  
S. Parakh ◽  
J. D. Atkin
Keyword(s):  
Neurodegenerative Diseases ◽  
Er Stress ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Therapeutic Interventions ◽  
Oxidative And Nitrosative Stress ◽  
Protective Function ◽  
Protein Disulphide Isomerase

Neurodegenerative diseases involve the progressive loss of neurons, and a pathological hallmark is the presence of abnormal inclusions containing misfolded proteins. Although the precise molecular mechanisms triggering neurodegeneration remain unclear, endoplasmic reticulum (ER) stress, elevated oxidative and nitrosative stress, and protein misfolding are important features in pathogenesis. Protein disulphide isomerase (PDI) is the prototype of a family of molecular chaperones and foldases upregulated during ER stress that are increasingly implicated in neurodegenerative diseases. PDI catalyzes the rearrangement and formation of disulphide bonds, thus facilitating protein folding, and in neurodegeneration may act to ameliorate the burden of protein misfolding. However, an aberrant posttranslational modification of PDI, S-nitrosylation, inhibits its protective function in these conditions. S-nitrosylation is a redox-mediated modification that regulates protein function by covalent addition of nitric oxide- (NO-) containing groups to cysteine residues. Here, we discuss the evidence for abnormal S-nitrosylation of PDI (SNO-PDI) in neurodegeneration and how this may be linked to another aberrant modification of PDI, S-glutathionylation. Understanding the role of aberrant S-nitrosylation/S-glutathionylation of PDI in the pathogenesis of neurodegenerative diseases may provide insights into novel therapeutic interventions in the future.

Role of medicinal plants against neurodegenerative diseases

2021 ◽  
Vol 22 ◽  
Author(s):  
Ritika Luthra ◽  
Arpita Roy
Keyword(s):  
Medicinal Plants ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Inflammatory Responses ◽  
Vital Role ◽  
Significant Loss ◽  
Therapeutic Interventions ◽  
Inflammatory Stress

: Diseases with a significant loss of neurons, structurally and functionally are termed as neurodegenerative diseases. Due to the present therapeutic interventions and progressive nature of diseases, a variety of side effects have risen up, thus leading the patients to go for an alternative medication. The role of medicinal plants in such cases has been beneficial because of their exhibition via different cellular and molecular mechanisms. Alleviation in inflammatory responses, suppression of the functionary aspect of pro-inflammatory cytokines like a tumor, improvement in antioxidative properties is among few neuroprotective mechanisms of traditional plants. Variation in transcription and transduction pathways play a vital role in the preventive measures of plants in such diseases. Neurodegenerative diseases are generally caused by depletion of proteins, oxidative and inflammatory stress, environmental changes and so on, with aging being the most important cause. Natural compounds can be used in order to treat neurodegenerative diseases Medicinal plants such as Ginseng, Withania somnifera, Bacopa monnieri, Ginkgo biloba, etc. are some of the medicinal plants for prevention of neurological symptoms. This review deals with the use of different medicinal plants for the prevention of neurodegenerative diseases.

scholarly journals Neurodegenerative Diseases: Multifactorial Conformational Diseases and Their Therapeutic Interventions

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Saba Sheikh ◽  
Safia ◽  
Ejazul Haque ◽  
Snober S. Mir
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Conformational Diseases ◽  
Considerable Evidence ◽  
Recent Trends ◽  
Lateral Sclerosis

Neurodegenerative diseases are multifactorial debilitating disorders of the nervous system that affect approximately 30 millionindividuals worldwide. Neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and dysfunctional trafficking of proteins. Beside that, mitochondrial dysfunction, oxidative stress, and/or environmental factors strongly associated with age have also been implicated in causing neurodegeneration. After years of intensive research, considerable evidence has accumulated that demonstrates an important role of these factors in the etiology of common neurodegenerative diseases. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. However, in order to explore the therapeutic interventions directed towards treatment of neurodegenerative diseases, neuroscientists are now fully exploiting the data obtained from studies of these basic mechanisms that have gone awry. The novelty of these mechanisms represents a challenge to the identification of viable drug targets and biomarkers for early diagnosis of the diseases. In this paper, we are reviewing various aspects associated with the disease and the recent trends that may have an application for the treatment of the neurodegenerative disorders.

Purines and Pyrimidines: Metabolism, Function and Potential as therapeutic options in neurodegenerative diseases

2020 ◽  
Vol 21 ◽  
Author(s):  
Debanjan Kundu ◽  
Vikash Kumar Dubey
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Treatment Regimens ◽  
Loss Of Balance ◽  
Current Scenario ◽  
Unexplored Area ◽  
Molecular Origin ◽  
Purines And Pyrimidines

Abstract:: Various neurodegenerative disorders have molecular origin but some common molecular mechanisms. In the current scenario, there are very few treatment regimens present for advanced neurodegenerative diseases. In this context, there is an urgent need for alternate options in the form of natural compounds with an ameliorating effect on patients. There have been individual scattered experiments trying to identify potential values of various intracellular metabolites. Purines and Pyrimidines, which are vital molecules governing various aspects of cellular biochemical reactions, have been long sought as crucial candidates for the same, but there are still many questions that go unanswered. Some critical functions of these molecules associated with neuromodulation activities have been identified. They are also known to play a role in foetal neurodevelopment, but there is a lacuna in understanding their mechanisms. In this review, we have tried to assemble and identify the importance of purines and pyrimidines, connecting them with the prevalence of neurodegenerative diseases. The leading cause of this class of diseases is protein misfolding and the formation of amyloids. A direct correlation between loss of balance in cellular homeostasis and amyloidosis is yet an unexplored area. This review aims at bringing the current literature available under one umbrella serving as a foundation for further extensive research in this field of drug development in neurodegenerative diseases.

scholarly journals The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Synovial Fluid ◽  
Knee Joint ◽  
Human Serum ◽  
Synovial Membrane ◽  
Nitrosative Stress ◽  
Control Groups ◽  
Oxidative And Nitrosative Stress ◽  
And Oxidative Stress

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

scholarly journals ER stress and development of type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Feyza Engin
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Adaptive Responses ◽  
Β Cell ◽  
Cellular Homeostasis ◽  
Unfolded Protein

Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease.

scholarly journals Biophysical studies of protein misfolding and aggregation in in vivo models of Alzheimer's and Parkinson's diseases

2020 ◽  
Vol 53 ◽  
Author(s):  
Tessa Sinnige ◽  
Karen Stroobants ◽  
Christopher M. Dobson ◽  
Michele Vendruscolo
Keyword(s):  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Amyloid Β ◽  
Therapeutic Interventions ◽  
In Vivo Models ◽  
Disease Modifying Drugs ◽  
Parkinson’S Diseases ◽  
Protein Misfolding And Aggregation

Abstract Neurodegenerative disorders, including Alzheimer's (AD) and Parkinson's diseases (PD), are characterised by the formation of aberrant assemblies of misfolded proteins. The discovery of disease-modifying drugs for these disorders is challenging, in part because we still have a limited understanding of their molecular origins. In this review, we discuss how biophysical approaches can help explain the formation of the aberrant conformational states of proteins whose neurotoxic effects underlie these diseases. We discuss in particular models based on the transgenic expression of amyloid-β (Aβ) and tau in AD, and α-synuclein in PD. Because biophysical methods have enabled an accurate quantification and a detailed understanding of the molecular mechanisms underlying protein misfolding and aggregation in vitro, we expect that the further development of these methods to probe directly the corresponding mechanisms in vivo will open effective routes for diagnostic and therapeutic interventions.

scholarly journals Anthocyanins and Their Metabolites as Therapeutic Agents for Neurodegenerative Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 333 ◽  
Author(s):  
Aimee N. Winter ◽  
Paula C. Bickford
Keyword(s):  
Neurodegenerative Diseases ◽  
Nitrosative Stress ◽  
Therapeutic Potential ◽  
Stress Protein ◽  
Motor Impairments ◽  
Oxidative And Nitrosative Stress ◽  
Beneficial Effects ◽  
Neuronal Populations ◽  
Neurodegenerative Process ◽  
Lateral Sclerosis

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), are characterized by the death of neurons within specific regions of the brain or spinal cord. While the etiology of many neurodegenerative diseases remains elusive, several factors are thought to contribute to the neurodegenerative process, such as oxidative and nitrosative stress, excitotoxicity, endoplasmic reticulum stress, protein aggregation, and neuroinflammation. These processes culminate in the death of vulnerable neuronal populations, which manifests symptomatically as cognitive and/or motor impairments. Until recently, most treatments for these disorders have targeted single aspects of disease pathology; however, this strategy has proved largely ineffective, and focus has now turned towards therapeutics which target multiple aspects underlying neurodegeneration. Anthocyanins are unique flavonoid compounds that have been shown to modulate several of the factors contributing to neuronal death, and interest in their use as therapeutics for neurodegeneration has grown in recent years. Additionally, due to observations that the bioavailability of anthocyanins is low relative to that of their metabolites, it has been proposed that anthocyanin metabolites may play a significant part in mediating the beneficial effects of an anthocyanin-rich diet. Thus, in this review, we will explore the evidence evaluating the neuroprotective and therapeutic potential of anthocyanins and their common metabolites for treating neurodegenerative diseases.

Sign in / Sign up

Export Citation Format

Share Document