Melanie D. Sweeney

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UNLABELLED The blood-brain barrier (BBB) limits entry of blood-derived products, pathogens, and cells into the brain that is essential for normal neuronal functioning and information processing. Post-mortem tissue analysis indicates BBB damage in Alzheimer's disease (AD). The timing of BBB breakdown remains, however, elusive. Using an advanced dynamic(More)
Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells,(More)
The recent shortage of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) has led to an increased demand for alternative amphetamine-like drugs such as the synthetic cathinone, 4-methylmethcathinone (mephedrone). Despite the re-classification of mephedrone as a Class B restricted substance by the United Kingdom and restrictive legislation by the United(More)
Vascular insults can initiate a cascade of molecular events leading to neurodegeneration, cognitive impairment, and dementia. Here, we review the cellular and molecular mechanisms in cerebral blood vessels and the pathophysiological events leading to cerebral blood flow dysregulation and disruption of the neurovascular unit and the blood-brain barrier,(More)
Neurovascular dysfunction, including blood–brain barrier (BBB) breakdown and cerebral blood flow (CBF) dysregulation and reduction, are increasingly recognized to contribute to Alzheimer’s disease (AD). The spatial and temporal relationships between different pathophysiological events during preclinical stages of AD, including cerebrovascular dysfunction(More)
Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles and post-capillary venules. CNS pericytes are uniquely positioned in the neurovascular unit between endothelial cells, astrocytes and neurons. They integrate, coordinate and process signals from(More)
Platelet-derived growth factor receptor-β (PDGFRβ) is expressed in the brain by vascular mural cells-brain capillary pericytes and arterial vascular smooth muscle cells (VSMCs). Recent evidence shows that blood-brain barrier (BBB) disruption and increased permeability, especially in the hippocampus, positively correlates with elevated levels of soluble(More)
BIBR1532 is a highly specific telomerase inhibitor, although the molecular basis for inhibition is unknown. Here we present the crystal structure of BIBR1532 bound to Tribolium castaneum catalytic subunit of telomerase (tcTERT). BIBR1532 binds to a conserved hydrophobic pocket (FVYL motif) on the outer surface of the thumb domain. The FVYL motif is near(More)
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