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Neurodegenerative Diseases and Protein Quality Control System

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 1077

Special Issue Editor

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons in specific brain regions. A hallmark of these conditions is the accumulation of misfolded and aggregated proteins, which disrupt cellular functions and significantly contribute to neuronal death. To counteract this, cells deploy sophisticated quality control systems such as molecular chaperones, the ubiquitin–proteasome system, autophagy, and the unfolded protein response. These mechanisms are crucial for ensuring proper protein folding and function, thereby preventing the harmful accumulation of misfolded proteins. The degradation of these aggregates through cell-mediated, enzymatic, and other clearance pathways is equally vital in the context of neurodegenerative diseases. For example, in AD, the enzymes responsible for the production of aggregation-prone amyloid β peptides, as well as their clearance mechanisms, are closely linked to the disease’s onset and progression. Understanding the intricate relationship between protein aggregation, the protein quality control system, clearance, and neurodegeneration is essential for developing new therapeutic strategies.

This Special Issue is dedicated to exploring the protein quality control system in the context of neurodegenerative diseases. Our aim is to elucidate the underlying mechanisms and highlight potential therapeutic strategies that could prove instrumental in managing these debilitating conditions.

Dr. Abdullah Sheikh
Guest Editor

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Keywords

  • Alzheimer’s disease
  • Parkinson’s disease
  • amyotrophic lateral sclerosis
  • Huntington’s disease
  • autophagy
  • protein aggregation
  • ubiquitin–proteasome system
  • neurodegeneration
  • neuroinflammation
  • aggregated protein clearance

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Published Papers (1 paper)

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Research

16 pages, 13739 KiB  
Article
A Cationic Zn-Phthalocyanine Turns Alzheimer’s Amyloid β Aggregates into Non-Toxic Oligomers and Inhibits Neurotoxicity in Culture
by Abdullah Md. Sheikh, Shatera Tabassum, Shozo Yano, Fatema Binte Abdullah, Ruochen Wang, Takahisa Ikeue and Atsushi Nagai
Int. J. Mol. Sci. 2024, 25(16), 8931; https://doi.org/10.3390/ijms25168931 - 16 Aug 2024
Cited by 1 | Viewed by 685
Abstract
Amyloid β peptide (Aβ) aggregation and deposition are considered the main causes of Alzheimer’s disease. In a previous study, we demonstrated that anionic Zn-phthalocyanine (ZnPc) can interact with the Aβ peptide and inhibit the fibril-formation process. However, due to the inability of anionic [...] Read more.
Amyloid β peptide (Aβ) aggregation and deposition are considered the main causes of Alzheimer’s disease. In a previous study, we demonstrated that anionic Zn-phthalocyanine (ZnPc) can interact with the Aβ peptide and inhibit the fibril-formation process. However, due to the inability of anionic ZnPc to cross the intact blood–brain barrier, we decided to explore the interaction of cationic methylated Zn-phthalocyanine (cZnPc) with the peptide. Using a ThT fluorescence assay, we observed that cZnPc dose-dependently and time-dependently inhibited Aβ1-42 fibril levels under in vitro fibril-formation conditions. Electron microscopy revealed that it caused Aβ1-42 peptides to form small aggregates. Western blotting and dot immunoblot oligomer experiments demonstrated that cZnPc increased rather than decreased the levels of oligomers from the very early stages of incubation. A binding assay confirmed that cZnPc could bind with the peptide. Docking simulations indicated that the oligomer species of Aβ1-42 had a higher ability to interact with cZnPc. ANS fluorescence assay results indicated that cZnPc did not affect the hydrophobicity of the peptide. However, cZnPc significantly increased intrinsic tyrosine fluorescence of the peptide after 8 h of incubation in fibril-formation conditions. Importantly, cell culture experiments demonstrated that cZnPc did not exhibit any toxicity up to a concentration of 10 µM. Instead, it protected a neuronal cell line from Aβ1-42-induced toxicity. Thus, our results suggest that cZnPc can affect the aggregation process of Aβ1-42, rendering it non-toxic, which could be crucial for the therapy of Alzheimer’s disease. Full article
(This article belongs to the Special Issue Neurodegenerative Diseases and Protein Quality Control System)
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