Publications by authors named "Nhat T T Le"

Genetic prion diseases are caused by mutations in PRNP, which encodes the prion protein (PrP). Why these mutations are pathogenic, and how they alter the properties of PrP are poorly understood. We have consented and accessed 22 individuals of a multi-generational Israeli family harboring the highly penetrant E200K PRNP mutation and generated a library of induced pluripotent stem cells (iPSCs) representing nine carriers and four non-carriers.

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Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no effective treatment options. Previous work from our laboratory identified phenethylpiperidines as a novel class of anti-prion compounds. While working to identify the molecular target(s) of these molecules, we unexpectedly discovered ten novel antiprion compounds based on their known ability to bind to the sigma receptors, σR and σR, which are currently being tested as therapeutic or diagnostic targets for cancer and neuropsychiatric disorders.

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Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no treatment options. Previous work from our laboratory identified phenethyl piperidines as novel class of anti-prion compounds. While working to identify the molecular target(s) of these molecules, we unexpectedly discovered ten novel anti-prion compounds based on their known ability to bind to the sigma receptors, σ R and R, which are currently being tested as therapeutic or diagnostic targets for cancer and neuropsychiatric disorders.

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Mutations in cause amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerations. However, the mechanism by which the UBQLN2 mutations cause disease remains unclear. Alterations in proteins involved in autophagy are prominent in neuronal tissue of human ALS patients and in a transgenic P497S UBQLN2 mouse model of ALS/FTD, suggesting a pathogenic link.

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Although the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity.

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Synaptic degeneration is one of the earliest pathological correlates of prion disease, and it is a major determinant of the progression of clinical symptoms. However, the cellular and molecular mechanisms underlying prion synaptotoxicity are poorly understood. Previously, we described an experimental system in which treatment of cultured hippocampal neurons with purified PrPSc, the infectious form of the prion protein, induces rapid retraction of dendritic spines, an effect that is entirely dependent on expression of endogenous PrPC by the target neurons.

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Missense mutations in ubiquilin 2 (UBQLN2) cause ALS with frontotemporal dementia (ALS-FTD). Animal models of ALS are useful for understanding the mechanisms of pathogenesis and for preclinical investigations. However, previous rodent models carrying UBQLN2 mutations failed to manifest any sign of motor neuron disease.

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Obesity is a global health issue with obese patients requiring specialised diagnosis, treatment and care through the health service. The practical and social difficulties associated with medical imaging of obese patients are an increasingly common problem and it is currently unknown how student and qualified radiographers perceive and respond to these challenges. By better understanding challenges presented in providing quality imaging and care of imaging obese patients, education for both qualified and student radiographers can be enhanced.

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Transmissible spongiform encephalopathies (TSE) are a heterogeneous group of neurodegenerative disorders. The common feature of these diseases is the pathological conversion of the normal cellular prion protein (PrP(C)) into a β-structure-rich conformer-termed PrP(Sc). The latter can induce a self-perpetuating process leading to amplification and spreading of pathological protein assemblies.

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