Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
4.8
2.7
Journals
Brain Sciences
Special Issues
Polyglutamine (PolyQ) Disorders
share announcement

Polyglutamine (PolyQ) Disorders

A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (30 April 2017) | Viewed by 31618

Special Issue Editor

Dr. Edamakanti Chandrakanth Reddy

E-Mail Website
Guest Editor
Department of Neurology, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Ward 10-321, Chicago, IL 60611-4296, USA
Interests: molecular mechanism of neurodegenerations; therepeutic implicatoins; iPSCs-based disease modeling; antisense oligonucleotide (ASO) based therapy

Special Issue Information

Dear Colleagues,

The polyglutamine (PolyQ) expansion disease family encompasses at least nine heritable disorders, including Huntington disease (HD) and the spinocerebellar ataxias SCA1, SCA2, SCA3 (Machado-Joseph disease), SCA6, SCA7, SCA17, spinal bulbar muscular atrophy (SBMA), and dentatorubral-pallidoluysian atrophy. At the molecular level, diseases are results from the expansion of CAG repeat that codes for the glutamine tract. A pathological hallmark of disorders is progressive neurodegeneration with accumulation of mutant protein aggregates. It is still unknown if these aggregates are pathogenic or protective to the cells. It is widely believed that the gain of protein function is primary cause for pathological events.  From recent and intriguing findings, it is known that repeat associated non-ATG (RAN) translation and RNA gain of toxic functions (e.g., HD) also play a crucial role in determining pathology. In most PolyQ disorders, the severity of disease is inversely correlated with the length of the PolyQ repeat.

Even though mutant proteins express ubiquitously, the molecular mechanism behind the selective vulnerability of each disorder is unknown. Lack of knowledge regarding this phenomenon has hampered the study of disease pathogenesis, as well as the identification of biomarkers to monitor disease progression. Understanding the molecular dysfunctions which take place before disease onset is particularly relevant for therapeutic purposes, as a possible pharmacologic intervention targeting the pre-symptomatic stages of disease is more likely to prevent its later clinical manifestation.

Dr. Chandrakanth Edamakanti
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • CAG repeatlenth disorders
  • Spinocerebellar Ataxias
  • Atrophy of cerebellum
  • Huntington’s disease
  • Movement disorders
  • Spinal and bulbar muscular atrophy

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Review

578 KiB  
Review
Protein Misfolding and Aggregation as a Therapeutic Target for Polyglutamine Diseases
by Toshihide Takeuchi and Yoshitaka Nagai
Brain Sci. 2017, 7(10), 128; https://doi.org/10.3390/brainsci7100128 - 11 Oct 2017
Cited by 52 | Viewed by 14443
Abstract
The polyglutamine (polyQ) diseases, such as Huntington’s disease and several types of spinocerebellar ataxias, are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ tract in disease-causative proteins. Proteins with an abnormally expanded polyQ stretch undergo [...] Read more.
The polyglutamine (polyQ) diseases, such as Huntington’s disease and several types of spinocerebellar ataxias, are a group of inherited neurodegenerative diseases that are caused by an abnormal expansion of the polyQ tract in disease-causative proteins. Proteins with an abnormally expanded polyQ stretch undergo a conformational transition to β-sheet rich structure, which assemble into insoluble aggregates with β-sheet rich amyloid fibrillar structures and accumulate as inclusion bodies in neurons, eventually leading to neurodegeneration. Since misfolding and aggregation of the expanded polyQ proteins are the most upstream event in the most common pathogenic cascade of the polyQ diseases, they are proposed to be one of the most ideal targets for development of disease-modifying therapies for polyQ diseases. In this review, we summarize the current understanding of the molecular pathogenic mechanisms of the polyQ diseases, and introduce therapeutic approaches targeting misfolding and aggregation of the expanded polyQ proteins, which are not only effective on a wide spectrum of polyQ diseases, but also broadly correct the functional abnormalities of multiple downstream cellular processes affected in the aggregation process of polyQ proteins. We hope that in the near future, effective therapies are developed, to bring hope to many patients suffering from currently intractable polyQ diseases. Full article
(This article belongs to the Special Issue Polyglutamine (PolyQ) Disorders)
►▼ Show Figures

Figure 1

257 KiB  
Review
Cognitive Changes in the Spinocerebellar Ataxias Due to Expanded Polyglutamine Tracts: A Survey of the Literature
by Evelyn Lindsay and Elsdon Storey
Brain Sci. 2017, 7(7), 83; https://doi.org/10.3390/brainsci7070083 - 14 Jul 2017
Cited by 29 | Viewed by 5692
Abstract
The dominantly-inherited ataxias characterised by expanded polyglutamine tracts—spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA 8—have all been shown to result in various degrees of cognitive impairment. We survey the literature on the [...] Read more.
The dominantly-inherited ataxias characterised by expanded polyglutamine tracts—spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA 8—have all been shown to result in various degrees of cognitive impairment. We survey the literature on the cognitive consequences of each disorder, attempting correlation with their published neuropathological, magnetic resonance imaging (MRI) and clinical features. We suggest several psychometric instruments for assessment of executive function, whose results are unlikely to be confounded by visual, articulatory or upper limb motor difficulties. Finally, and with acknowledgement of the inadequacies of the literature to date, we advance a tentative classification of these disorders into three groups, based on the reported severity of their cognitive impairments, and correlated with their neuropathological topography and MRI findings: group 1—SCAs 6 and 8—mild dysexecutive syndrome based on disruption of cerebello-cortical circuitry; group 2—SCAs 1, 2, 3, and 7—more extensive deficits based largely on disruption of striatocortical in addition to cerebello-cerebral circuitry; and group 3—SCA 17 and DRPLA—in which cognitive impairment severe enough to cause a dementia syndrome is a frequent feature. Full article
(This article belongs to the Special Issue Polyglutamine (PolyQ) Disorders)
1032 KiB  
Review
Striatal Vulnerability in Huntington’s Disease: Neuroprotection Versus Neurotoxicity
by Ryoma Morigaki and Satoshi Goto
Brain Sci. 2017, 7(6), 63; https://doi.org/10.3390/brainsci7060063 - 7 Jun 2017
Cited by 49 | Viewed by 9752
Abstract
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium [...] Read more.
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat encoding an abnormally long polyglutamine tract (PolyQ) in the huntingtin (Htt) protein. In HD, striking neuropathological changes occur in the striatum, including loss of medium spiny neurons and parvalbumin-expressing interneurons accompanied by neurodegeneration of the striosome and matrix compartments, leading to progressive impairment of reasoning, walking and speaking abilities. The precise cause of striatal pathology in HD is still unknown; however, accumulating clinical and experimental evidence suggests multiple plausible pathophysiological mechanisms underlying striatal neurodegeneration in HD. Here, we review and discuss the characteristic neurodegenerative patterns observed in the striatum of HD patients and consider the role of various huntingtin-related and striatum-enriched proteins in neurotoxicity and neuroprotection. Full article
(This article belongs to the Special Issue Polyglutamine (PolyQ) Disorders)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop