Role of Ubiquitin Protein Ligases in the Pathogenesis of Polyglutamine Diseases

2007 ◽  
Vol 33 (5) ◽  
pp. 945-951 ◽  
Author(s):  
Priyanka Dikshit ◽  
Nihar Ranjan Jana
Keyword(s):  
Polyglutamine Diseases ◽  
Protein Ligases

The ubiquitin-proteasome system in cardiac physiology and pathology

2006 ◽  
Vol 291 (1) ◽  
pp. H1-H19 ◽  
Author(s):  
Saul R. Powell
Keyword(s):  
Protein Turnover ◽  
Protein Quality ◽  
Ubiquitin Proteasome System ◽  
Intracellular Protein ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Intracellular Protein Degradation ◽  
Ubiquitin Proteasome ◽  
Protein Ligases

The ubiquitin-proteasome system (UPS) is the major nonlysosomal pathway for intracellular protein degradation, generally requiring a covalent linkage of one or more chains of polyubiquitins to the protein intended for degradation. It has become clear that the UPS plays major roles in regulating many cellular processes, including the cell cycle, immune responses, apoptosis, cell signaling, and protein turnover under normal and pathological conditions, as well as in protein quality control by removal of damaged, oxidized, and/or misfolded proteins. This review will present an overview of the structure, biochemistry, and physiology of the UPS with emphasis on its role in the heart, if known. In addition, evidence will be presented supporting the role of certain muscle-specific ubiquitin protein ligases, key regulatory components of the UPS, in regulation of sarcomere protein turnover and cardiomyocyte size and how this might play a role in induction of the hypertrophic phenotype. Moreover, this review will present the evidence suggesting that proteasomal dysfunction may play a role in cardiac pathologies such as myocardial ischemia, congestive heart failure, and myofilament-related and idiopathic-dilated cardiomyopathies, as well as cardiomyocyte loss in the aging heart. Finally, certain pitfalls of proteasome studies will be described with the intent of providing investigators with enough information to avoid these problems. This review should provide current investigators in the field with an up-to-date analysis of the literature and at the same time provide an impetus for new investigators to enter this important and rapidly changing area of research.

scholarly journals Possible Role of the Transglutaminases in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Antonio Martin ◽  
Giulia De Vivo ◽  
Vittorio Gentile
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Therapeutic Effects ◽  
Polyglutamine Diseases ◽  
Post Translational Modification ◽  
Transglutaminase Activity

Transglutaminases are ubiquitous enzymes which catalyze posttranslational modifications of proteins. Recently, transglutaminase-catalyzed post-translational modification of proteins has been shown to be involved in the molecular mechanisms responsible for human diseases. Transglutaminase activity has been hypothesized to be involved also in the pathogenetic mechanisms responsible for several human neurodegenerative diseases. Alzheimer's disease and other neurodegenerative diseases, such as 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. This paper focuses on the possible molecular mechanisms by which transglutaminase activity could be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases, and on the possible therapeutic effects of selective transglutaminase inhibitors for the cure of patients with diseases characterized by aberrant transglutaminase activity.

scholarly journals The Role of Vesicle Trafficking Defects in the Pathogenesis of Prion and Prion-Like Disorders

2020 ◽  
Vol 21 (19) ◽  
pp. 7016
Author(s):  
Pearl Cherry ◽  
Sabine Gilch
Keyword(s):  
Neurodegenerative Diseases ◽  
Prion Diseases ◽  
Primary Component ◽  
Vesicular Trafficking ◽  
Polyglutamine Diseases ◽  
Amyloid Aggregates ◽  
The Common ◽  
Trafficking Defects ◽  
Insight Into

Prion diseases are fatal and transmissible neurodegenerative diseases in which the cellular form of the prion protein ‘PrPc’, misfolds into an infectious and aggregation prone isoform termed PrPSc, which is the primary component of prions. Many neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and polyglutamine diseases, such as Huntington’s disease, are considered prion-like disorders because of the common characteristics in the propagation and spreading of misfolded proteins that they share with the prion diseases. Unlike prion diseases, these are non-infectious outside experimental settings. Many vesicular trafficking impairments, which are observed in prion and prion-like disorders, favor the accumulation of the pathogenic amyloid aggregates. In addition, many of the vesicular trafficking impairments that arise in these diseases, turn out to be further aggravating factors. This review offers an insight into the currently known vesicular trafficking defects in these neurodegenerative diseases and their implications on disease progression. These findings suggest that these impaired trafficking pathways may represent similar therapeutic targets in these classes of neurodegenerative disorders.

The Role of Mutant RNA in the Pathogenesis of Huntington’s Disease and Other Polyglutamine Diseases

2019 ◽  
Vol 53 (6) ◽  
pp. 838-849 ◽  
Author(s):  
A. N. Bogomazova ◽  
A. V. Eremeev ◽  
G. E. Pozmogova ◽  
M. A. Lagarkova
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Polyglutamine Diseases

scholarly journals High Rates of Genome Rearrangements and Pathogenicity of Shigella spp.

2021 ◽  
Vol 12 ◽  
Author(s):  
Zaira Seferbekova ◽  
Alexey Zabelkin ◽  
Yulia Yakovleva ◽  
Robert Afasizhev ◽  
Natalia O. Dranenko ◽  
...  
Keyword(s):  
Homologous Recombination ◽  
Synteny Block ◽  
Genome Rearrangements ◽  
Genomic Islands ◽  
E Coli ◽  
Coding Regions ◽  
Shigella Spp ◽  
High Level ◽  
Protein Ligases

Shigella are pathogens originating within the Escherichia lineage but frequently classified as a separate genus. Shigella genomes contain numerous insertion sequences (ISs) that lead to pseudogenisation of affected genes and an increase of non-homologous recombination. Here, we study 414 genomes of E. coli and Shigella strains to assess the contribution of genomic rearrangements to Shigella evolution. We found that Shigella experienced exceptionally high rates of intragenomic rearrangements and had a decreased rate of homologous recombination compared to pathogenic and non-pathogenic E. coli. The high rearrangement rate resulted in independent disruption of syntenic regions and parallel rearrangements in different Shigella lineages. Specifically, we identified two types of chromosomally encoded E3 ubiquitin-protein ligases acquired independently by all Shigella strains that also showed a high level of sequence conservation in the promoter and further in the 5′-intergenic region. In the only available enteroinvasive E. coli (EIEC) strain, which is a pathogenic E. coli with a phenotype intermediate between Shigella and non-pathogenic E. coli, we found a rate of genome rearrangements comparable to those in other E. coli and no functional copies of the two Shigella-specific E3 ubiquitin ligases. These data indicate that the accumulation of ISs influenced many aspects of genome evolution and played an important role in the evolution of intracellular pathogens. Our research demonstrates the power of comparative genomics-based on synteny block composition and an important role of non-coding regions in the evolution of genomic islands.

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