Intracerebral seeding of amyloid-β and tau pathology in mice: Factors underlying prion-like spreading and comparisons with α-synuclein

McAllister, Brendan B.; Lacoursiere, Sean G.; Sutherland, Robert J.; Mohajerani, Majid H.

doi:10.1016/j.neubiorev.2020.01.026

Cited by 36 publications

(31 citation statements)

References 216 publications

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“…As a further common mechanism associated with altered protein degradation in these diseases, the hypothesis of a prion-like protein propagation has been proposed [14,22,[29][30][31][32][33][34][35][36]. This is supported by evidence that, similar to the prion protein and its misfolded scrapie isoform, undigested, misfold-prone proteins such as α-syn, tau, Aβ, huntingtin, SOD-1, TDP-43 and FUS can form intracellular aggregates in a self-templating manner [37][38][39][40][41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Limanaqi

Biagioni

Gambardella

et al. 2020

IJMS

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Alterations in autophagy and the ubiquitin proteasome system (UPS) are commonly implicated in protein aggregation and toxicity which manifest in a number of neurological disorders. In fact, both UPS and autophagy alterations are bound to the aggregation, spreading and toxicity of the so-called prionoid proteins, including alpha synuclein (α-syn), amyloid-beta (Aβ), tau, huntingtin, superoxide dismutase-1 (SOD-1), TAR-DNA-binding protein of 43 kDa (TDP-43) and fused in sarcoma (FUS). Recent biochemical and morphological studies add to this scenario, focusing on the coordinated, either synergistic or compensatory, interplay that occurs between autophagy and the UPS. In fact, a number of biochemical pathways such as mammalian target of rapamycin (mTOR), transcription factor EB (TFEB), Bcl2-associated athanogene 1/3 (BAG3/1) and glycogen synthase kinase beta (GSk3β), which are widely explored as potential targets in neurodegenerative proteinopathies, operate at the crossroad between autophagy and UPS. These biochemical steps are key in orchestrating the specificity and magnitude of the two degradation systems for effective protein homeostasis, while intermingling with intracellular secretory/trafficking and inflammatory pathways. The findings discussed in the present manuscript are supposed to add novel viewpoints which may further enrich our insight on the complex interactions occurring between cell-clearing systems, protein misfolding and propagation. Discovering novel mechanisms enabling a cross-talk between the UPS and autophagy is expected to provide novel potential molecular targets in proteinopathies.

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Section: Introductionmentioning

confidence: 99%

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Limanaqi

Biagioni

Gambardella

et al. 2020

IJMS

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“…The induced deposits and cerebral angiopathy were detected by immunohistochemistry, Congo red, and silver staining [25,27]. Seeding has similarly been shown to accelerate pathology caused by the misfolding of tau and α-synuclein in mouse models (reviewed in [28][29][30]). In this review, we focus on the variables at play in manipulating Aβ deposition in APP transgenic mice by seeding.…”

Section: Introductionmentioning

confidence: 99%

Remodeling Alzheimer-amyloidosis models by seeding

Ulm

Borchelt

Moore

2021

Mol Neurodegeneration

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Alzheimer’s disease (AD) is among the most prevalent neurodegenerative diseases, with brain pathology defined by extracellular amyloid beta deposits and intracellular tau aggregates. To aid in research efforts to improve understanding of this disease, transgenic murine models have been developed that replicate aspects of AD pathology. Familial AD is associated with mutations in the amyloid precursor protein and in the presenilins (associated with amyloidosis); transgenic amyloid models feature one or more of these mutant genes. Recent advances in seeding methods provide a means to alter the morphology of resultant amyloid deposits and the age that pathology develops. In this review, we discuss the variety of factors that influence the seeding of amyloid beta pathology, including the source of seed, the time interval after seeding, the nature of the transgenic host, and the preparation of the seeding inoculum.

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“…In this review regarding amyloid cross-interactions, we decided to mainly focus on the direct interaction between Aβ and Tau, highlighting what is emerged in the last years. Since a very recent and detailed review about the in vivo intracerebral seeding of Aβ and Tau in mice [72], has just been released, we will mainly focus on the in vitro studies aiming to deepen the knowledge about the physicochemical aspects of this interaction. The growing interest in understanding the cross-seeded interaction between Aβ and Tau is justified by several in vivo experiments showing that Aβ enhances Tau pathology by increasing the formation of Tau species capable of seeding new aggregates [73][74][75][76][77][78][79][80].…”

Section: Tau Proteinmentioning

confidence: 99%

The Positive Side of the Alzheimer’s Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1

et al. 2020

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Alzheimer’s disease (AD) represents a progressive amyloidogenic disorder whose advancement is widely recognized to be connected to amyloid-β peptides and Tau aggregation. However, several other processes likely contribute to the development of AD and some of them might be related to protein-protein interactions. Amyloid aggregates usually contain not only single type of amyloid protein, but also other type of proteins and this phenomenon can be rationally explained by the process of protein cross-seeding and co-assembly. Amyloid cross-interaction is ubiquitous in amyloid fibril formation and so a better knowledge of the amyloid interactome could help to further understand the mechanisms of amyloid related diseases. In this review, we discuss about the cross-interactions of amyloid-β peptides, and in particular Aβ1-42, with other amyloids, which have been presented either as integrated part of Aβ neurotoxicity process (such as Tau) or conversely with a preventive role in AD pathogenesis by directly binding to Aβ (such as transthyretin, cystatin C and apolipoprotein A1). Particularly, we will focus on all the possible therapeutic strategies aiming to rescue the Aβ toxicity by taking inspiration from these protein-protein interactions.

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Intracerebral seeding of amyloid-β and tau pathology in mice: Factors underlying prion-like spreading and comparisons with α-synuclein

Cited by 36 publications

References 216 publications

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies

Remodeling Alzheimer-amyloidosis models by seeding

The Positive Side of the Alzheimer’s Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1

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