scholarly journals Possibilities of Combinatorial Therapy: Insulin Dysregulation and the Growth Hormone Perspective on Neurodegeneration

2021 ◽  
Author(s):  
Priyanka Sengupta ◽  
Debashis Mukhopadhyay
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Neurodegenerative Diseases ◽  
Insulin Receptor ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Combinatorial Therapy ◽  
Insulin Pathway ◽  
Insulin Dysregulation ◽  
Receptor Family

RTKs have been reported to be implicated in several neurodegenerative disorders and the roles of insulin receptor family have emerged as a key common pathway across diseases. Thus we focussed on the Insulin receptor family and discussed the irregulation from the growth hormone axis. The signaling, regulation and physiology of the production in liver and CNS has never been discussed in signaling perspectives and is extremely crucial for understanding the possibilities of IGF1 in neurodegeneration specifically. The commonalities across neurodegenerative diseases such as oxidative stress, mitochondrial dysfunction, and protein misfolding and insulin pathway anomalies have been elucidated and correlated with the insulin pathway. The crosstalk possibilities of the pathways, along with other regulatory modes for the development of combinatorial therapy have been discussed to visualize a common platform for neurodegenerative diseases including AD, PD, HD, ALS and FTD. Furthermore, the incretin based therapies that have gradually emerged as alternatives for insulin based therapy due to its inherent drawback of resistance has been briefly discussed.

scholarly journals Reactive Oxygen Species in Neurodegenerative Diseases: Implications in Pathogenesis and Treatment Strategies

2021 ◽  
Author(s):  
Johnson Olaleye Oladele ◽  
Adenike T. Oladiji ◽  
Oluwaseun Titilope Oladele ◽  
Oyedotun M. Oyeleke
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Critical Role ◽  
Treatment Strategies ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
The Brain

Neurodegenerative diseases are debilitating disorders which compromise motor or cognitive functions and are rapidly becoming a global communal disorder with over 46.8 million people suffering dementia worldwide. Aetiological studies have showed that people who are exposed to agricultural, occupational and environmental toxic chemicals that can interfere and degenerate dopaminergic neurons are prone to developing neurodegenerative diseases such as Parkinson Disease. The complex pathogenesis of the neurodegenerative diseases remains largely unknown; however, mounting evidence suggests that oxidative stress, neuroinflammation, protein misfolding, and apoptosis are the hallmarks of the diseases. Reactive oxygen species (ROS) are chemically reactive molecules that have been implicated in the pathogenesis of neurodegenerative diseases. ROS play a critical role as high levels of oxidative stress are commonly observed in the brain of patients with neurodegenerative disorders. This chapter focus on the sources of ROS in the brain, its involvement in the pathogenesis of neurodegenerative diseases and possible ways to mitigate its damaging effects in the affected brain.

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 Disulfide Bonding in Neurodegenerative Misfolding Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Maria Francesca Mossuto
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Disulfide Bonds ◽  
Protein Misfolding ◽  
Bond Formation ◽  
Specific Protein ◽  
Disulfide Bonding ◽  
Misfolding Diseases ◽  
Protein Misfolding And Aggregation

In recent years an increasing number of neurodegenerative diseases has been linked to the misfolding of a specific protein and its subsequent accumulation into aggregated species, often toxic to the cell. Of all the factors that affect the behavior of these proteins, disulfide bonds are likely to be important, being very conserved in protein sequences and being the enzymes devoted to their formation among the most conserved machineries in mammals. Their crucial role in the folding and in the function of a big fraction of the human proteome is well established. The role of disulfide bonding in preventing and managing protein misfolding and aggregation is currently under investigation. New insights into their involvement in neurodegenerative diseases, their effect on the process of protein misfolding and aggregation, and into the role of the cellular machineries devoted to disulfide bond formation in neurodegenerative diseases are emerging. These studies mark a step forward in the comprehension of the biological base of neurodegenerative disorders and highlight the numerous questions that still remain open.

scholarly journals POTENTIAL USE OF SULFORAPHANE AS A NEUROPROTECTOR

2021 ◽  
pp. 125-136
Author(s):  
S. A. Tsiumpala ◽  
K. M. Starchevska ◽  
V. I. Lushchak
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Old Age ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
The Body ◽  
Biologically Active ◽  
Inflammatory Processes ◽  
The Brain ◽  
Potential Use

Introduction. Under normal conditions, oxidative stress and proinflammatory processes are tightly controlled. However, during neuroinflammation and overproduction of reactive oxygen species (ROS), homeostasis is disrup­ted, which may lead to development of Alzheimer’s disease, Parkinson’s disease and other neurodegenerative disorders. Inflammatory processes may result in neurodegenerative disorders. Sulforaphane is an isothiocyanate compound which has potential for treatment of neurodegenerative disorders. Its therapeutic potential is based on the ability to activate transcription of genes, that regulate protective cellular mechanisms. The importance of stu­dying sulforaphane as a neuroprotector is based on the fact, that dementias are the seventh leading cause of death glo­bally and actively progress due to aging of human population. In this review, the anti-inflammatory effects of sulforaphane in the brain and its use as a potential neuroprotector in the treatment of neurodegenerative diseases are discussed. The aim of the study – to review available literature sources on the potential use of sulforaphane to prevent or mitigate neuroinflammation. Conclusions. Economic and technological development of mankind and the improvement of the general qua­lity of life leads to prolongation of human life. But, achievements of longevity give new challenges to humanity. In young age and early adulthood, the organisms can relatively easily maintain homeostasis, then in old age intensification of oxidative stress and inflammatory processes can lead to the development of dementias and mental disorders. What should we do now to save clear mind in old age? In this review, sulforaphane is considered to be a potential neuroprotector. Biologically active supplements and drugs containing sulforaphane can weaken up inflammatory processes in the brain and in the body in general, and therefore they can be used for prevention and treatment of neurodegenerative diseases.

scholarly journals Review on various factors responsible for neurodegenerative disorders

2021 ◽  
Vol 16 (1) ◽  
pp. 126-132
Author(s):  
Harshwardhan J Tembhurnikar ◽  
Neha D Thool ◽  
Rasika J Patil ◽  
Ranjita K Das
Keyword(s):  
Oxidative Stress ◽  
Nervous System ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Critical Role ◽  
Structure And Function ◽  
Neuronal Structure ◽  
Pathophysiological Mechanisms ◽  
Neurological Illnesses ◽  
And Function

Neurodegenerative disorders are nervous system disorders that result in the loss of neuronal structure and function. As shown in Alzheimer's and Parkinson's disease, these changes cause a loss of various capacities, including cognition and mobility. Several factors have been discovered to play a critical role in the etiology of common neurological illnesses, including oxidative stress and protein misfolding. It's still unclear if these factors cause or contribute to the progression of the illnesses. Despite efforts to understand the molecular and pathophysiological mechanisms behind these pathways, many aspects remain unknown. The goal of this review is to investigate the numerous factors linked to neurodegeneration.

scholarly journals The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

2018 ◽  
Vol 19 (12) ◽  
pp. 3824 ◽  
Author(s):  
Anuradha Tarafdar ◽  
Giordano Pula
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Ros Generation ◽  
Phagocytic Cells ◽  
Nadph Oxidases ◽  
Age Related ◽  
Recent Developments ◽  
Cerebrovascular Endothelial Cells

For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation—primarily superoxide anion (O2●−), although hydrogen peroxide (H2O2) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.

scholarly journals Molecular mechanisms of proteinopathies across neurodegenerative disease: a review

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Alexander P. Marsh
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disease ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Molecular Mechanisms ◽  
Current Data ◽  
Main Body ◽  
Molecular Events ◽  
Underlying Pathology

Abstract Background Although there is a range of different symptoms across neurodegenerative diseases, they have been noted to have common pathogenic features. An archetypal feature shared between these diseases is protein misfolding; however, the mechanism behind the proteins abnormalities is still under investigation. There is an emerging hypothesis in the literature that the mechanisms that lead to protein misfolding may be shared across neurodegenerative processes, suggesting a common underlying pathology. Main body This review discusses the literature to date of the shared features of protein misfolding, failures in proteostasis, and potential propagation pathways across the main neurodegenerative disorders. Conclusion The current data suggests, despite overarching processes being shared, that the molecular events implicated in protein pathology are distinct across common neurodegenerative disorders.

scholarly journals Proteostasis Failure in Neurodegenerative Diseases: Focus on Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Annika Höhn ◽  
Antonella Tramutola ◽  
Roberta Cascella
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Protein Quality ◽  
Cellular Protein ◽  
Protein Levels ◽  
A Cell ◽  
Lysosomal System ◽  
Turn Over ◽  
Protein Dysfunction

Protein homeostasis or proteostasis is an essential balance of cellular protein levels mediated through an extensive network of biochemical pathways that regulate different steps of the protein quality control, from the synthesis to the degradation. All proteins in a cell continuously turn over, contributing to development, differentiation, and aging. Due to the multiple interactions and connections of proteostasis pathways, exposure to stress conditions may cause various types of protein damage, altering cellular homeostasis and disrupting the entire network with additional cellular stress. Furthermore, protein misfolding and/or alterations during protein synthesis results in inactive or toxic proteins, which may overload the degradation mechanisms. The maintenance of a balanced proteome, preventing the formation of impaired proteins, is accomplished by two major catabolic routes: the ubiquitin proteasomal system (UPS) and the autophagy-lysosomal system. The proteostasis network is particularly important in nondividing, long-lived cells, such as neurons, as its failure is implicated with the development of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. These neurological disorders share common risk factors such as aging, oxidative stress, environmental stress, and protein dysfunction, all of which alter cellular proteostasis, suggesting that general mechanisms controlling proteostasis may underlay the etiology of these diseases. In this review, we describe the major pathways of cellular proteostasis and discuss how their disruption contributes to the onset and progression of neurodegenerative diseases, focusing on the role of oxidative stress.

Dysregulation of Transcription Factors: A Key Culprit Behind Neurodegenerative Disorders

2018 ◽  
Vol 25 (6) ◽  
pp. 548-565
Author(s):  
Wei Jin ◽  
Talal Jamil Qazi ◽  
Zhenzhen Quan ◽  
Nuomin Li ◽  
Hong Qing
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Clinical Manifestations ◽  
Pathological Changes ◽  
Expression Of Genes ◽  
Protein Molecules ◽  
Neuronal Systems

Neurodegenerative diseases (NDs) are considered heterogeneous disorders characterized by progressive pathological changes in neuronal systems. Transcription factors are protein molecules that are important in regulating the expression of genes. Although the clinical manifestations of NDs vary, the pathological processes appear similar with regard to neuroinflammation, oxidative stress, and proteostasis, to which, as numerous studies have discovered, transcription factors are closely linked. In this review, we summarized and reviewed the roles of transcription factors in NDs, and then we elucidated their functions during pathological processes, and finally we discussed their therapeutic values in NDs.

scholarly journals Interaction between -Synuclein and Other Proteins in Neurodegenerative Disorders

2011 ◽  
Vol 11 ◽  
pp. 1893-1907 ◽  
Author(s):  
Kurt A. Jellinger
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Synergistic Effects ◽  
Amyloid Β ◽  
Hyperphosphorylated Tau ◽  
Clinical Genetic ◽  
Neuroscience Research ◽  
Misfolding Diseases

Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.

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