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 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.

scholarly journals Hsp90 and Its Co-Chaperones in Neurodegenerative Diseases

2019 ◽  
Vol 20 (20) ◽  
pp. 4976 ◽  
Author(s):  
Anastasiia Bohush ◽  
Paweł Bieganowski ◽  
Anna Filipek
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Functional Activity ◽  
Protein Misfolding ◽  
Three Dimensional ◽  
Heat Shock Protein 90 ◽  
Eukaryotic Cells

Proper folding is crucial for proteins to achieve functional activity in the cell. However, it often occurs that proteins are improperly folded (misfolded) and form aggregates, which are the main hallmark of many diseases including cancers, neurodegenerative diseases and many others. Proteins that assist other proteins in proper folding into three-dimensional structures are chaperones and co-chaperones. The key role of chaperones/co-chaperones is to prevent protein aggregation, especially under stress. An imbalance between chaperone/co-chaperone levels has been documented in neurons, and suggested to contribute to protein misfolding. An essential protein and a major regulator of protein folding in all eukaryotic cells is the heat shock protein 90 (Hsp90). The function of Hsp90 is tightly regulated by many factors, including co-chaperones. In this review we summarize results regarding the role of Hsp90 and its co-chaperones in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and prionopathies.

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.

Folding of peptides and proteins: role of disulfide bonds, recent developments

2013 ◽  
Vol 4 (6) ◽  
pp. 597-604 ◽  
Author(s):  
Yuji Hidaka ◽  
Shigeru Shimamoto
Keyword(s):  
Protein Folding ◽  
Disulfide Bonds ◽  
Bond Formation ◽  
Difficult Problem ◽  
Chemical Methods ◽  
Mutant Proteins ◽  
Folding Intermediates ◽  
Peptide Chemistry ◽  
Recent Developments

AbstractDisulfide-containing proteins are ideal models for studies of protein folding as the folding intermediates can be observed, trapped, and separated by HPLC during the folding reaction. However, regulating or analyzing the structures of folding intermediates of peptides and proteins continues to be a difficult problem. Recently, the development of several techniques in peptide chemistry and biotechnology has resulted in the availability of some powerful tools for studying protein folding in the context of the structural analysis of native, mutant proteins, and folding intermediates. In this review, recent developments in the field of disulfide-coupled peptide and protein folding are discussed, from the viewpoint of chemical and biotechnological methods, such as analytical methods for the detection of disulfide pairings, chemical methods for disulfide bond formation between the defined Cys residues, and applications of diselenide bonds for the regulation of disulfide-coupled peptide and protein folding.

Prions and Neurodegenerative Diseases: A Focus on Alzheimer’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Alessio Crestini ◽  
Francesca Santilli ◽  
Stefano Martellucci ◽  
Elena Carbone ◽  
Maurizio Sorice ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Amyloid Β ◽  
Specific Protein ◽  
Cellular Prion Protein ◽  
Aβ Oligomers ◽  
The Central Nervous System ◽  
Induced Signal

Specific protein misfolding and aggregation are mechanisms underlying various neurodegenerative diseases such as prion disease and Alzheimer’s disease (AD). The misfolded proteins are involved in prions, amyloid-β (Aβ), tau, and α-synuclein disorders; they share common structural, biological, and biochemical characteristics, as well as similar mechanisms of aggregation and self-propagation. Pathological features of AD include the appearance of plaques consisting of deposition of protein Aβ and neurofibrillary tangles formed by the hyperphosphorylated tau protein. Although it is not clear how protein aggregation leads to AD, we are learning that the cellular prion protein (PrPC) plays an important role in the pathogenesis of AD. Herein, we first examined the pathogenesis of prion and AD with a focus on the contribution of PrPC to the development of AD. We analyzed the mechanisms that lead to the formation of a high affinity bond between Aβ oligomers (AβOs) and PrPC. Also, we studied the role of PrPC as an AβO receptor that initiates an AβO-induced signal cascade involving mGluR5, Fyn, Pyk2, and eEF2K linking Aβ and tau pathologies, resulting in the death of neurons in the central nervous system. Finally, we have described how the PrPC-AβOs interaction can be used as a new potential therapeutic target for the treatment of PrPC-dependent AD.

scholarly journals Mechanistic Insights into the Role of Molecular Chaperones in Protein Misfolding Diseases: From Molecular Recognition to Amyloid Disassembly

2020 ◽  
Vol 21 (23) ◽  
pp. 9186
Author(s):  
Rubén Hervás ◽  
Javier Oroz
Keyword(s):  
Molecular Chaperones ◽  
Protein Misfolding ◽  
Cell Damage ◽  
Protective Role ◽  
Soluble Proteins ◽  
Protein Deposits ◽  
Client Proteins ◽  
Recognition Motifs ◽  
Misfolding Diseases

Age-dependent alterations in the proteostasis network are crucial in the progress of prevalent neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, or amyotrophic lateral sclerosis, which are characterized by the presence of insoluble protein deposits in degenerating neurons. Because molecular chaperones deter misfolded protein aggregation, regulate functional phase separation, and even dissolve noxious aggregates, they are considered major sentinels impeding the molecular processes that lead to cell damage in the course of these diseases. Indeed, members of the chaperome, such as molecular chaperones and co-chaperones, are increasingly recognized as therapeutic targets for the development of treatments against degenerative proteinopathies. Chaperones must recognize diverse toxic clients of different orders (soluble proteins, biomolecular condensates, organized protein aggregates). It is therefore critical to understand the basis of the selective chaperone recognition to discern the mechanisms of action of chaperones in protein conformational diseases. This review aimed to define the selective interplay between chaperones and toxic client proteins and the basis for the protective role of these interactions. The presence and availability of chaperone recognition motifs in soluble proteins and in insoluble aggregates, both functional and pathogenic, are discussed. Finally, the formation of aberrant (pro-toxic) chaperone complexes will also be disclosed.

scholarly journals Therapeutic Potential of AAV1-Rheb(S16H) Transduction against Neurodegenerative Diseases

2021 ◽  
Vol 22 (6) ◽  
pp. 3064
Author(s):  
Youngpyo Nam ◽  
Gyeong Joon Moon ◽  
Sang Ryong Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Active Form ◽  
Mammalian Target Of Rapamycin ◽  
Regulatory System ◽  
Neuronal Population ◽  
Vital Role

Neurotrophic factors (NTFs) are essential for cell growth, survival, synaptic plasticity, and maintenance of specific neuronal population in the central nervous system. Multiple studies have demonstrated that alterations in the levels and activities of NTFs are related to the pathology and symptoms of neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease. Hence, the key molecule that can regulate the expression of NTFs is an important target for gene therapy coupling adeno-associated virus vector (AAV) gene. We have previously reported that the Ras homolog protein enriched in brain (Rheb)–mammalian target of rapamycin complex 1 (mTORC1) axis plays a vital role in preventing neuronal death in the brain of AD and PD patients. AAV transduction using a constitutively active form of Rheb exerts a neuroprotective effect through the upregulation of NTFs, thereby promoting the neurotrophic interaction between astrocytes and neurons in AD conditions. These findings suggest the role of Rheb as an important regulator of the regulatory system of NTFs to treat neurodegenerative diseases. In this review, we present an overview of the role of Rheb in neurodegenerative diseases and summarize the therapeutic potential of AAV serotype 1 (AAV1)-Rheb(S16H) transduction in the treatment of neurodegenerative disorders, focusing on diseases, such as AD and PD.

scholarly journals Nanoimaging for Protein Misfolding Diseases. Critical Role of Misfolded Dimers in the Amyloid Self-Assembly

2011 ◽  
Vol 17 (S2) ◽  
pp. 170-171
Author(s):  
A Krasnoslobodtsev ◽  
B-H Kim ◽  
Y Lyubchenko
Keyword(s):  
Self Assembly ◽  
Protein Misfolding ◽  
Critical Role ◽  
Misfolding Diseases

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011.

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.

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