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Full-Text Articles in Medicine and Health Sciences
Evidence For A Partially Folded Intermediate In Α-Synuclein Fibril Formation, Vladimir N. Uversky, Jie Li, Anthony L. Fink
Evidence For A Partially Folded Intermediate In Α-Synuclein Fibril Formation, Vladimir N. Uversky, Jie Li, Anthony L. Fink
Molecular Medicine Faculty Publications
Intracellular proteinaceous aggregates (Lewy bodies and Lewy neurites) of α-synuclein are hallmarks of neurodegenerative diseases such as Parkinson's disease, dementia with Lewy bodies, and multiple systemic atrophy. However, the molecular mechanisms underlying α-synuclein aggregation into such filamentous inclusions remain unknown. An intriguing aspect of this problem is that α-synuclein is a natively unfolded protein, with little or no ordered structure under physiological conditions. This raises the question of how an essentially disordered protein is transformed into highly organized fibrils. In the search for an answer to this question, we have investigated the effects of pH and temperature on the structural …
Is Congo Red An Amyloid-Specific Dye?, Ritu Khurana, Vladimir N. Uversky, Liza Nielsen, Anthony L. Fink
Is Congo Red An Amyloid-Specific Dye?, Ritu Khurana, Vladimir N. Uversky, Liza Nielsen, Anthony L. Fink
Molecular Medicine Faculty Publications
Congo red (CR) binding, monitored by characteristic yellow-green birefringence under crossed polarization has been used as a diagnostic test for the presence of amyloid in tissue sections for several decades. This assay is also widely used for the characterization of in vitro amyloid fibrils. In order to probe the structural specificity of Congo red binding to amyloid fibrils we have used an induced circular dichroism (CD) assay. Amyloid fibrils from insulin and the variable domain of Ig light chain demonstrate induced CD spectra upon binding to Congo red. Surprisingly, the native conformations of insulin and Ig light chain also induced …
Metal-Triggered Structural Transformations, Aggregation, And Fibrillation Of Human Α-Synuclein: A Possible Molecular Link Between Parkinson′S Disease And Heavy Metal Exposure, Vladimir N. Uversky, Jie Li, Anthony L. Fink
Metal-Triggered Structural Transformations, Aggregation, And Fibrillation Of Human Α-Synuclein: A Possible Molecular Link Between Parkinson′S Disease And Heavy Metal Exposure, Vladimir N. Uversky, Jie Li, Anthony L. Fink
Molecular Medicine Faculty Publications
Parkinson's disease involves the aggregation of α-synuclein to form fibrils, which are the major constituent of intracellular protein inclusions (Lewy bodies and Lewy neurites) in dopaminergic neurons of the substantia nigra. Occupational exposure to specific metals, especially manganese, copper, lead, iron, mercury, zinc, aluminum, appears to be a risk factor for Parkinson's disease based on epidemiological studies. Elevated levels of several of these metals have also been reported in the substantia nigra of Parkinson's disease subjects. We examined the effect of various metals on the kinetics of fibrillation of recombinant α-synuclein and in inducing conformational changes, as monitored by biophysical …
Stabilization Of Partially Folded Conformation During Α-Synuclein Oligomerization In Both Purified And Cytosolic Preparations, Vladimir N. Uversky, He-Jin Lee, Jie Li, Anthony L. Fink, Seung-Jae Lee
Stabilization Of Partially Folded Conformation During Α-Synuclein Oligomerization In Both Purified And Cytosolic Preparations, Vladimir N. Uversky, He-Jin Lee, Jie Li, Anthony L. Fink, Seung-Jae Lee
Molecular Medicine Faculty Publications
Aggregation of α-synuclein is tightly associated with many neurodegenerative diseases, such as Parkinson's disease, dementia with Lewy body, Lewy body variant of Alzheimer's disease, multiple system atrophy, and Hallervorden-Spatz disease, implicating a crucial role of aggregated forms of α-synuclein in the pathogenesis. Here, we examined the effect of elevated temperature on the oligomerization and structural changes of α-synuclein in the early stage of aggregation and show that self-assembly is crucial for the stabilization of a partially folded conformation. The efficiency of α-synuclein oligomerization increased proportional to the temperature increase, both in purified form and in crude cytosolic preparation. This oligomerization …
Cannabinoids And The Immune System, Thomas W. Klein, Catherine A. Newton, Herman Friedman
Cannabinoids And The Immune System, Thomas W. Klein, Catherine A. Newton, Herman Friedman
Molecular Medicine Faculty Publications
The effect of cannabimimetic agents on the function of immune cells such as T and B lymphocytes, natural killer cells and macrophages has been extensively studied over the past several decades using human and animal paradigms involving whole animal models as well as tissue culture systems. From this work, it can be concluded that these drugs have subtle yet complex effects on immune cell function and that some of the drug activity is mediated by cannabinoid receptors expressed on the various immune cell subtypes. However, the overall role of the cannabinoid system of receptors and ligands in human health and …