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Brain Sciences
Special Issues
Protein Post-Translational Modifications and Protein Aaggregation in Neurodegenerative Diseases
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Protein Post-Translational Modifications and Protein Aaggregation in Neurodegenerative Diseases

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (25 March 2020) | Viewed by 15963

Special Issue Editor

Dr. Wayne Carter

E-Mail Website1 Website2
Guest Editor
Clinical Toxicology, School of Medicine, The University of Nottingham, Nottingham NG7 2RD, UK
Interests: biomedicines; neurotoxicity; neurodegeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Many, if not all proteins, undergo post-translational modification(s) (PTMs). Protein PTMs impinge upon local and global protein structure and thereby influence protein function. Protein PTMs may have desired functional outcomes such as enzymatic activation, but can also contribute to the propensity for protein aggregation. Undesired or aberrant protein aggregation is common to a number of neurodegenerative diseases, with accumulation of aggregated proteins thought to be neurotoxic. Examples include; Aβ or tau protein aggregates in Alzheimer’s disease; α-synuclein deposits within Lewy bodies (LBs) in Parkinson’s disease, multiple system atrophy, and dementia with LBs; and poly-glutamine tracts in Huntington’s disease. A growing area of research in neurodegenerative disease focusses upon how PTMs promote protein aggregation, and how modified and aggregated proteins may be resistant to degradation or removal by cellular machinery including proteasomal or autophagic mechanisms. The importance of protein PTMs and associated protein aggregation are underscored by current clinical research to develop drugs or biological therapies with anti-(protein)aggregation properties. This special issue will broadly cover PTMs that may influence protein aggregation, methods to detect aggregated proteins, and the relationship between protein aggregation and the pathogenesis or progression of neurodegenerative diseases.

Dr. Wayne Carter
Guest Editor

Keywords

  • protein aggregation
  • protein post-translational modifications
  • neurotoxicity
  • neurodegeneration
  • Alzheimer's disease
  • Parkinson's disease

Published Papers (2 papers)

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18 pages, 14778 KiB  
Article
Colocalization of BRCA1 with Tau Aggregates in Human Tauopathies
by Masanori Kurihara, Tatsuo Mano, Yuko Saito, Shigeo Murayama, Tatsushi Toda and Atsushi Iwata
Brain Sci. 2020, 10(1), 7; https://doi.org/10.3390/brainsci10010007 - 20 Dec 2019
Cited by 18 | Viewed by 5619
Abstract
The mechanism of neuronal dysfunction via tau aggregation in tauopathy patients is controversial. In Alzheimer’s disease (AD), we previously reported mislocalization of the DNA repair nuclear protein BRCA1, its coaggregation with tau, and the possible importance of the subsequent DNA repair dysfunction. However, [...] Read more.
The mechanism of neuronal dysfunction via tau aggregation in tauopathy patients is controversial. In Alzheimer’s disease (AD), we previously reported mislocalization of the DNA repair nuclear protein BRCA1, its coaggregation with tau, and the possible importance of the subsequent DNA repair dysfunction. However, whether this dysfunction in BRCA1 also occurs in other tauopathies is unknown. The aim of this study was to evaluate whether BRCA1 colocalizes with tau aggregates in the cytoplasm in the brains of the patients with tauopathy. We evaluated four AD, two Pick’s disease (PiD), three progressive supranuclear palsy (PSP), three corticobasal degeneration (CBD), four normal control, and four disease control autopsy brains. Immunohistochemistry was performed using antibodies against BRCA1 and phosphorylated tau (AT8). Colocalization was confirmed by immunofluorescence double staining. Colocalization of BRCA1 with tau aggregates was observed in neurofibrillary tangles and neuropil threads in AD, pick bodies in PiD, and globose neurofibrillary tangles and glial coiled bodies in PSP. However, only partial colocalization was observed in tuft-shaped astrocytes in PSP, and no colocalization was observed in CBD. Mislocalization of BRCA1 was not observed in disease controls. BRCA1 was mislocalized to the cytoplasm and colocalized with tau aggregates in not only AD but also in PiD and PSP. Mislocalization of BRCA1 by tau aggregates may be involved in the pathogenesis of PiD and PSP. Full article
(This article belongs to the Special Issue Protein Post-Translational Modifications and Protein Aaggregation in Neurodegenerative Diseases)
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Review

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30 pages, 4747 KiB  
Review
Do Post-Translational Modifications Influence Protein Aggregation in Neurodegenerative Diseases: A Systematic Review
by Larissa-Nele Schaffert and Wayne G. Carter
Brain Sci. 2020, 10(4), 232; https://doi.org/10.3390/brainsci10040232 - 11 Apr 2020
Cited by 80 | Viewed by 9765
Abstract
The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate [...] Read more.
The accumulation of abnormal protein aggregates represents a universal hallmark of neurodegenerative diseases (NDDs). Post-translational modifications (PTMs) regulate protein structure and function. Dysregulated PTMs may influence the propensity for protein aggregation in NDD-proteinopathies. To investigate this, we systematically reviewed the literature to evaluate effects of PTMs on aggregation propensity for major proteins linked to the pathogenesis and/or progression of NDDs. A search of PubMed, MEDLINE, EMBASE, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between PTMs and protein aggregation in seven NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxias, transmissible spongiform encephalopathy, and multiple sclerosis. Together, 1222 studies were identified, of which 69 met eligibility criteria. We identified that the following PTMs, in isolation or combination, potentially act as modulators of proteinopathy in NDDs: isoaspartate formation in Aβ, phosphorylation of Aβ or tau in AD; acetylation, 4-hydroxy-2-neonal modification, O-GlcNAcylation or phosphorylation of α-synuclein in PD; acetylation or phosphorylation of TAR DNA-binding protein-43 in ALS, and SUMOylation of superoxide dismutase-1 in ALS; and phosphorylation of huntingtin in HD. The potential pharmacological manipulation of these aggregation-modulating PTMs represents an as-yet untapped source of therapy to treat NDDs. Full article
(This article belongs to the Special Issue Protein Post-Translational Modifications and Protein Aaggregation in Neurodegenerative Diseases)
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