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Amyloid Toxicity in Alzheimer's Disease
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Amyloid Toxicity in Alzheimer's Disease

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 10035

Special Issue Editor

Prof. Dr. Patrizia Hrelia

E-Mail Website
Guest Editor
Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy
Interests: neurodegeneration; neuroprotection; natural compounds; Alzheimer’s disease; Parkinson’s disease

Special Issue Information

Dear Colleagues,

Alzheimer’s disease (AD) represents the most common cause of cognitive impairments in the aging population. Indeed, AD is primarily a sporadic disorder, and fewer than 5% of cases appear associated with familial inheritance. Thus, the identification of toxins that accumulate with aging in the AD brain and the aberrant signaling pathways that lead to synapse dysfunction is undoubtedly essential to discovering successful new successful therapeutic approaches. The accumulation of amyloid plaques by the aggregation of the amyloid-β (Aβ) peptide and the formation of neurofibrillary tangles are widely accepted as the main neuropathological hallmarks of AD pathology. Increasing evidence has indicated that AD is characterized by a heightened oxidative environment in the brain, and the accumulation of Aβ increases oxidative stress and leads to mitochondrial dysfunction and energy failure even in the early stages of AD. The amyloid hypothesis suggests Aβ as being responsible for the development of AD. However, the exact mechanism by which Aβ causes neuronal toxicity and cognitive impairment is not yet clearly understood.

In this Special Issue, “Amyloid Toxicity in Alzheimer’s Disease”, we invite investigators to contribute original research articles and review articles regarding the neuronal toxicity induced by Aβ, its role in aging and AD, and new potential strategies to counteract its accumulation.

Prof. Dr. Patrizia Hrelia
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Published Papers (3 papers)

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Research

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11 pages, 1358 KiB  
Article
Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation
by Toshisuke Kaku, Kaori Tsukakoshi and Kazunori Ikebukuro
Int. J. Mol. Sci. 2021, 22(23), 12780; https://doi.org/10.3390/ijms222312780 - 26 Nov 2021
Cited by 3 | Viewed by 1689
Abstract
Significant research on Alzheimer’s disease (AD) has demonstrated that amyloid β (Aβ) oligomers are toxic molecules against neural cells. Thus, determining the generation mechanism of toxic Aβ oligomers is crucial for understanding AD pathogenesis. Aβ fibrils were reported to be disaggregated by treatment [...] Read more.
Significant research on Alzheimer’s disease (AD) has demonstrated that amyloid β (Aβ) oligomers are toxic molecules against neural cells. Thus, determining the generation mechanism of toxic Aβ oligomers is crucial for understanding AD pathogenesis. Aβ fibrils were reported to be disaggregated by treatment with small compounds, such as epigallocatechin gallate (EGCG) and dopamine (DA), and a loss of fibril shape and decrease in cytotoxicity were observed. However, the characteristics of intermediate products during the fibril disaggregation process are poorly understood. In this study, we found that cytotoxic Aβ aggregates are generated during a moderate disaggregation process of Aβ fibrils. A cytotoxicity assay revealed that Aβ fibrils incubated with a low concentration of EGCG and DA showed higher cytotoxicity than Aβ fibrils alone. Atomic force microscopy imaging and circular dichroism spectrometry showed that short and narrow protofilaments, which were highly stable in the β-sheet structure, were abundant in these moderately disaggregated samples. These results indicate that toxic Aβ protofilaments are generated during disaggregation from amyloid fibrils, suggesting that disaggregation of Aβ fibrils by small compounds may be one of the possible mechanisms for the generation of toxic Aβ aggregates in the brain. Full article
(This article belongs to the Special Issue Amyloid Toxicity in Alzheimer's Disease)
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13 pages, 2258 KiB  
Article
Aggregation Mechanism of Alzheimer’s Amyloid β-Peptide Mediated by α-Strand/α-Sheet Structure
by Anand Balupuri, Kwang-Eun Choi and Nam Sook Kang
Int. J. Mol. Sci. 2020, 21(3), 1094; https://doi.org/10.3390/ijms21031094 - 07 Feb 2020
Cited by 14 | Viewed by 4002
Abstract
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and a widespread form of dementia. Aggregated forms of the amyloid β-peptide (Aβ) are identified as a toxic species responsible for neuronal damage in AD. Extensive research has been conducted to reveal [...] Read more.
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and a widespread form of dementia. Aggregated forms of the amyloid β-peptide (Aβ) are identified as a toxic species responsible for neuronal damage in AD. Extensive research has been conducted to reveal the aggregation mechanism of Aβ. However, the structure of pathological aggregates and the mechanism of aggregation are not well understood. Recently, experimental studies have confirmed that the α-sheet structure in Aβ drives aggregation and toxicity in AD. However, how the α-sheet structure is formed in Aβ and how it contributes to Aβ aggregation remains elusive. In the present study, molecular dynamics simulations suggest that Aβ adopts the α-strand conformation by peptide-plane flipping. Multiple α-strands interact through hydrogen bonding to form α-sheets. This structure acts as a nucleus that initiates and promotes aggregation and fibrillation of Aβ. Our findings are supported by previous experimental as well as theoretical studies. This study provides valuable structural insights for the design of anti-AD drugs exploiting the α-strand/α-sheet structure. Full article
(This article belongs to the Special Issue Amyloid Toxicity in Alzheimer's Disease)
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Review

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14 pages, 2906 KiB  
Review
NLRP3 and Infections: β-Amyloid in Inflammasome beyond Neurodegeneration
by Giulia Sita, Agnese Graziosi, Patrizia Hrelia and Fabiana Morroni
Int. J. Mol. Sci. 2021, 22(13), 6984; https://doi.org/10.3390/ijms22136984 - 29 Jun 2021
Cited by 21 | Viewed by 3577
Abstract
Amyloid beta (Aβ)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer’s disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus [...] Read more.
Amyloid beta (Aβ)-induced abnormal neuroinflammation is recognized as a major pathological feature of Alzheimer’s disease (AD), which results in memory impairment. Research exploring low-grade systemic inflammation and its impact on the development and progression of neurodegenerative disease has increased. A particular research focus has been whether systemic inflammation arises only as a secondary effect of disease, or it is also a cause of pathology. The inflammasomes, and more specifically the NLRP3 inflammasome, are crucial components of the innate immune system and are usually activated in response to infection or tissue damage. Although inflammasome activation plays critical roles against various pathogens in host defense, overactivation of inflammasome contributes to the pathogenesis of inflammatory diseases, including acute central nervous system (CNS) injuries and chronic neurodegenerative diseases, such as AD. This review summarizes the current literature on the role of the NLRP3 inflammasome in the pathogenesis of AD, and its involvement in infections, particularly SARS-CoV-2. NLRP3 might represent the crossroad between the hypothesized neurodegeneration and the primary COVID-19 infection. Full article
(This article belongs to the Special Issue Amyloid Toxicity in Alzheimer's Disease)
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