David Westaway
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View article: Expression of progerin enhances disease-related endpoints in a tau seeding reporter cell system
Expression of progerin enhances disease-related endpoints in a tau seeding reporter cell system Open
Sporadic Alzheimer’s disease and some forms of frontotemporal lobar degeneration (FTLD-tau) are neurological disorders of later life where cognitive deficits follow from the progressive accumulation of microtubule-associated tau protein. D…
View article: Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar Degeneration
Microbial Composition, Disease Trajectory and Genetic Background in a Slow Onset Model of Frontotemporal Lobar Degeneration Open
Slow-onset neurodegenerative disease in a low-expresser 2N4R P301L transgenic (Tg) mouse model is marked by neuroinflammation and by differing patterns of CNS deposition and accumulation of tau conformers, with such heterogeneities present…
View article: Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease
Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease Open
Highly abundant in neurons, the cellular prion protein (PrP C ) is an obligatory precursor to the disease‐associated misfolded isoform denoted PrP Sc that accumulates in the rare neurodegenerative disorders referred to either as transmissi…
View article: Application of N-Terminal Labeling Methods Provide Novel Insights into Endoproteolysis of the Prion Protein <i>in Vivo</i>
Application of N-Terminal Labeling Methods Provide Novel Insights into Endoproteolysis of the Prion Protein <i>in Vivo</i> Open
Alternative α- and β-cleavage events in the cellular prion protein (PrPC) central region generate fragments with distinct biochemical features that affect prion disease pathogenesis, but the assignment of precise cleavage positions has pro…
View article: Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein
Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein Open
The cellular prion protein (PrP C ) converts to alternatively folded pathogenic conformations (PrP Sc ) in prion infections and binds neurotoxic oligomers formed by amyloid-β α-synuclein, and tau. β-Endoproteolysis, which splits PrP C into…
View article: The effect of Aβ seeding is dependent on the presence of knock-in genes in the AppNL−G−F mice
The effect of Aβ seeding is dependent on the presence of knock-in genes in the AppNL−G−F mice Open
Alzheimer's disease (AD) is characterized by the prion-like propagation of amyloid-β (Aβ). However, the role of Aβ in cognitive impairment is still unclear. To determine the causal role of Aβ in AD, we intracerebrally seeded the entorhinal…
View article: Investigating CRISPR/Cas9 gene drive for production of disease-preventing prion gene alleles
Investigating CRISPR/Cas9 gene drive for production of disease-preventing prion gene alleles Open
Prion diseases are a group of fatal neurodegenerative disorders that includes chronic wasting disease, which affects cervids and is highly transmissible. Given that chronic wasting disease prevalence exceeds 30% in some endemic areas of No…
View article: Amyloid-β seeding effects are dependent on the presence of knock-in genes in the App<sup>NL-G-F</sup> mice
Amyloid-β seeding effects are dependent on the presence of knock-in genes in the App<sup>NL-G-F</sup> mice Open
Alzheimer’s disease (AD) is characterized by the prion-like propagation of amyloid-β (Aβ). However, the role of Aβ in cognitive impairment is still unclear. To determine the causal role of Aβ in AD, we intracerebrally seeded the entorhinal…
View article: Susceptibility of Beavers to Chronic Wasting Disease
Susceptibility of Beavers to Chronic Wasting Disease Open
Chronic wasting disease (CWD) is a contagious, fatal, neurodegenerative prion disease of cervids. The expanding geographical range and rising prevalence of CWD are increasing the risk of pathogen transfer and spillover of CWD to non-cervid…
View article: Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer’s disease
Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer’s disease Open
Rapid replication in vitro implicates distinct populations of misfolded hippocampal 4R TAU protein in accelerated progression of Alzheimer’s disease.
View article: Lipid rafts act as a common platform for Aß oligomer-induced Alzheimer’s pathology
Lipid rafts act as a common platform for Aß oligomer-induced Alzheimer’s pathology Open
Background Amyloid ß protein (Aß) oligomers induce the overproduction of phosphorylated tau and neurodegeneration. These cascades gradually cause cognitive impairment in Alzheimer’s disease (AD). While each pathological event in AD has bee…
View article: Genetic Depletion of Amylin/Calcitonin Receptors Improves Memory and Learning in Transgenic Alzheimer’s Disease Mouse Models.
Genetic Depletion of Amylin/Calcitonin Receptors Improves Memory and Learning in Transgenic Alzheimer’s Disease Mouse Models. Open
Based upon its interactions with amyloid β peptide (Aβ), the amylin receptor, a Class B G protein-coupled receptor (GPCR), is a potential modulator of Alzheimer’s disease (AD) pathogenesis. However, past pharmacological approaches have fai…
View article: Multisite interactions of prions with membranes and native nanodiscs
Multisite interactions of prions with membranes and native nanodiscs Open
Although prions are known as protein-only infectious particles, they exhibit lipid specificities, cofactor dependencies and membrane-dependent activities. Such membrane interactions play key roles in how prions are processed, presented and…
View article: Cellular Biology of Tau Diversity and Pathogenic Conformers
Cellular Biology of Tau Diversity and Pathogenic Conformers Open
Tau accumulation is a prominent feature in a variety of neurodegenerative disorders and remarkable effort has been expended working out the biochemistry and cell biology of this cytoplasmic protein. Tau's wayward properties may derive from…
View article: Tau Conformers in FTLD-MAPT&nbsp; Undergo Liquid-liquid Phase Separation and Perturb the Nuclear Envelope
Tau Conformers in FTLD-MAPT Undergo Liquid-liquid Phase Separation and Perturb the Nuclear Envelope Open
Background: Germline mutations in the MAPT gene cause some forms of frontotemporal lobar degeneration (FTLD). Recent studies show that a single mutation in MAPT can promote alternative tau misfolding pathways engendering divergent tau conf…
View article: Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against β‐amyloid‐toxicity
Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against β‐amyloid‐toxicity Open
Background Evidence suggests that amyloid β (Aβ) peptides play an important role in the degeneration of neurons during the development of Alzheimer's disease (AD), the prevalent cause of dementia affecting the elderly. The endosomal–lysoso…
View article: Tau conformers in FTLD-MAPT undergo liquid-liquid phase separation and perturb the nuclear envelope
Tau conformers in FTLD-MAPT undergo liquid-liquid phase separation and perturb the nuclear envelope Open
Recent studies show that a single MAPT gene mutation can promote alternative tau misfolding pathways engendering divergent forms of frontotemporal dementia and that under conditions of molecular crowding, the repertoire of tau forms can in…
View article: Teaching case 3-2019: Are nuclear clefts or invaginations the niche of intranuclear inclusions in FTLD-TDP?
Teaching case 3-2019: Are nuclear clefts or invaginations the niche of intranuclear inclusions in FTLD-TDP? Open
No abstract available.