The role of amyloid oligomers in neurodegenerative pathologies

Wells, Cameron I.; Brennan, Samuel; Keon, Matt; Ooi, Lezanne

doi:10.1016/j.ijbiomac.2021.03.113

Cited by 74 publications

(68 citation statements)

References 269 publications

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“…Thus, PrP rather than individual disease-associated proteins might be (immuno)therapeutically targeted. Moreover, a few additional molecular targets have been reported in the literature, e.g., TAR DNA-binding protein 43 (TDP-43), dipeptide repeat proteins (DPRs), superoxide dismutase 1, and huntingtin protein [1,14,18,31,32], but little data on the development of vaccines against these targets are available. [3].…”

Section: Biomolecular Targets Of Vaccines For Neurodegenerative Diseasesmentioning

confidence: 99%

“…In addition to PD, α-syn has been lately associated with AD, too [17]. Misfolding/accumulation of additional proteins, e.g., superoxide dismutase 1 and huntingtin, in specific brain regions has been related to the onset/progress of neurodegenerative diseases, such as ALS and HD, respectively [1,14,18]. To further support the linkage between certain proteins/peptides and neurodegenerative diseases, focusing on AD, we should mention that cerebrospinal fluid (CSF) levels of Aβ-and tau-related biomarkers have been widely employed for confirming AD diagnosis, along with positive amyloid-PET scans [5,19].…”

Section: Introductionmentioning

confidence: 99%

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Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

et al. 2021

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The development of peptide-based vaccines for treating human neurodegenerative diseases has been the eventual aim of many research endeavors, although no active immunotherapies have been approved for clinical use till now. A typical example of such endeavors is the effort to develop vaccines for Alzheimer’s disease based on the beta-amyloid peptide, which continues to be intensively investigated despite previous setbacks. In this paper, recent developments in peptide-based vaccines which target beta-amyloid as well as tau protein and α-synuclein are presented. Particular focus has been directed toward peptide epitopes and formulation systems selected/developed and employed to enhance vaccine efficacy and safety. Results from both, human clinical trials and animal preclinical studies conducted mainly in transgenic mice have been included. Future perspectives on the topic are also briefly discussed.

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Section: Biomolecular Targets Of Vaccines For Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

et al. 2021

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“…Of particular interest are secondary nucleation reactions including fibril surface-catalyzed formation of new clusters of monomers [31] and fibril fragmentation into smaller pieces [32]. Both secondary processes seem crucial in the formation of additional aggregation intermediates [33], which are the main cytotoxic species of the amyloid formation process [34].…”

Section: Synucleinopathies and α-Synuclein Amyloid Formationmentioning

confidence: 99%

“…The toxic function of amyloids primarily arises from the intermediate oligomeric species that populate the aggregation process [34]. Their higher hydrophobicity and smaller size, which results in a high diffusion coefficient, allow them to establish aberrant interactions with different cellular components and spread more readily [2].…”

Section: Human Disaggregase In Amyloid Toxicity and Propagation: Friend And Foementioning

confidence: 99%

Unzipping the Secrets of Amyloid Disassembly by the Human Disaggregase

Franco

Velasco-Carneros

Alvarez

et al. 2021

Cells

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Neurodegenerative diseases (NDs) are increasingly positioned as leading causes of global deaths. The accelerated aging of the population and its strong relationship with neurodegeneration forecast these pathologies as a huge global health problem in the upcoming years. In this scenario, there is an urgent need for understanding the basic molecular mechanisms associated with such diseases. A major molecular hallmark of most NDs is the accumulation of insoluble and toxic protein aggregates, known as amyloids, in extracellular or intracellular deposits. Here, we review the current knowledge on how molecular chaperones, and more specifically a ternary protein complex referred to as the human disaggregase, deals with amyloids. This machinery, composed of the constitutive Hsp70 (Hsc70), the class B J-protein DnaJB1 and the nucleotide exchange factor Apg2 (Hsp110), disassembles amyloids of α-synuclein implicated in Parkinson’s disease as well as of other disease-associated proteins such as tau and huntingtin. We highlight recent studies that have led to the dissection of the mechanism used by this chaperone system to perform its disaggregase activity. We also discuss whether this chaperone-mediated disassembly mechanism could be used to solubilize other amyloidogenic substrates. Finally, we evaluate the implications of the chaperone system in amyloid clearance and associated toxicity, which could be critical for the development of new therapies.

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“…Age-associated neurodegenerative diseases, including Alzheimer’s, Parkinson’s and prion diseases are linked to the toxicity caused by protein misfolding, particularly into amyloid fold ( 1 ). For example, brains of Alzheimer’s disease patients commonly display β-amyloid and/or neurofibrillary tangles of tau that accumulate outside and inside neurons, spread between cells and thereby disrupt normal cell functions.…”

Section: Main Textmentioning

confidence: 99%

A rare natural lipid induces neuroglobin expression to prevent amyloid oligomers toxicity and retinal neurodegeneration

Knuckles

et al. 2021

Preprint

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Most neurodegenerative diseases such as Alzheimer's disease are proteinopathies linked to the toxicity of amyloid oligomers. Treatments to delay or cure these diseases are lacking. Using budding yeast, we report that the natural lipid tripentadecanoin induces expression of the nitric oxide oxidoreductase Yhb1 to prevent the formation of protein aggregates during aging and extends replicative lifespan. In mammals, tripentadecanoin induces expression of the Yhb1 orthologue, neuroglobin, to protect neurons against amyloid toxicity. Tripentadecanoin also rescues photoreceptors in a mouse model of retinal degeneration and retinal ganglion cells in a Rhesus monkey model of optic atrophy. Together, we propose that tripentadecanoin affects p-bodies to induce neuroglobin expression and offers a potential treatment for proteinopathies and retinal neurodegeneration.

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The role of amyloid oligomers in neurodegenerative pathologies

Cited by 74 publications

References 269 publications

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

Unzipping the Secrets of Amyloid Disassembly by the Human Disaggregase

A rare natural lipid induces neuroglobin expression to prevent amyloid oligomers toxicity and retinal neurodegeneration

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