21 research outputs found

    Post translational changes to α-synuclein control iron and dopamine trafficking : a concept for neuron vulnerability in Parkinson's disease

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    Parkinson's disease is a multifactorial neurodegenerative disorder, the aetiology of which remains elusive. The primary clinical feature of progressively impaired motor control is caused by a loss of midbrain substantia nigra dopamine neurons that have a high α-synuclein (α-syn) and iron content. α-Syn is a neuronal protein that is highly modified post-translationally and central to the Lewy body neuropathology of the disease. This review provides an overview of findings on the role post translational modifications to α-syn have in membrane binding and intracellular vesicle trafficking. Furthermore, we propose a concept in which acetylation and phosphorylation of α-syn modulate endocytic import of iron and vesicle transport of dopamine during normal physiology. Disregulated phosphorylation and oxidation of α-syn mediate iron and dopamine dependent oxidative stress through impaired cellular location and increase propensity for α-syn aggregation. The proposition highlights a connection between α-syn, iron and dopamine, three pathological components associated with disease progression in sporadic Parkinson's disease

    Predicting expository text processing : causal content density as a critical expository text metric

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    202106 bcvcNot applicableSelf-fundedEarly release18 month

    Slow Delayed Rectifier Potassium Current (IKs) and the Repolarization Reserve

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    The aim of this review is to present the properties of the slow component of the delayed rectifier potassium current (I-Ks) in the human ventricle. The review gives a detailed description of the physiology, molecular biology and pharmacology of the I-Ks current, including kinetic properties, genetic structures, agonists and antagonists. The authors also present the role of the I-Ks current in the human cardiac repolarization focusing on several pathophysiological situations, such as the LQT syndrome and the Torsade de Pointes arrhythmia
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