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Full-Text Articles in Medicine and Health Sciences
Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas
Α-Synuclein Fibrils As Penrose Machines: A Chameleon In The Gear, Francesca De Giorgi, Vladimir N. Uversky, François Ichas
Molecular Medicine Faculty Publications
In 1957, Lionel Penrose built the first man-made self-replicating mechanical device and illustrated its function in a series of machine prototypes, prefiguring our current view of the genesis and the proliferation of amyloid fibrils. He invented and demonstrated, with the help of his son Roger, the concepts that decades later, would become the fundamentals of prion and prion-like neurobiology: nucleation, seeding and conformational templating of monomers, linear polymer elongation, fragmentation, and spread. He published his premonitory discovery in a movie he publicly presented at only two conferences in 1958, a movie we thus reproduce here. By making a 30-year-jump in …
Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney
Ferritinophagy And Α-Synuclein: Pharmacological Targeting Of Autophagy To Restore Iron Regulation In Parkinson’S Disease, Matthew K. Boag, Angus Roberts, Vladimir N. Uversky, Linlin Ma, Des R. Richardson, Dean L. Pountney
Molecular Medicine Faculty Publications
A major hallmark of Parkinson’s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated …
Biophysical Characterization Of Α-Synuclein And Rotenone Interaction, Blanca A. Silva, Olöf Einarsdóttir, Anthony L. Fink, Vladimir N. Uversky
Biophysical Characterization Of Α-Synuclein And Rotenone Interaction, Blanca A. Silva, Olöf Einarsdóttir, Anthony L. Fink, Vladimir N. Uversky
Molecular Medicine Faculty Publications
Previous studies revealed that pesticides interact with α-synuclein and accelerate the rate of fibrillation. These results are consistent with the prevailing hypothesis that the direct interaction of α-synuclein with pesticides is one of many suspected factors leading to α-synuclein fibrillation and ultimately to Parkinson's disease. In this study, the biophysical properties and fibrillation kinetics of α-synuclein in the presence of rotenone were investigated and, more specifically, the effects of rotenone on the early-stage misfolded forms of α-synuclein were considered. The thioflavine T (ThT) fluorescence assay studies provide evidence that early-phase misfolded α-synuclein forms are affected by rotenone and that the …
Modulating Α-Synuclein Misfolding And Fibrillation In Vitro By Agrochemicals, Blanca A. Silva, Olöf Einarsdóttir, Anthony L. Fink, Vladimir N. Uversky
Modulating Α-Synuclein Misfolding And Fibrillation In Vitro By Agrochemicals, Blanca A. Silva, Olöf Einarsdóttir, Anthony L. Fink, Vladimir N. Uversky
Molecular Medicine Faculty Publications
A combination of spectroscopic techniques including atomic force microscopy (AFM) and transmission electron microscopy (TEM), was used to analyze the effect of chemically distinct agrochemicals (pesticides, herbicides, and fungicides) on the in vitro misfolding and aggregation of a presynaptic intrinsically disordered protein α-synuclein. Despite their differences in chemical properties, almost all the compounds screened affected the α-synuclein fibrillation in a concentration-dependent manner. The morphology of the aggregated α-synuclein was characterized by AFM and TEM techniques. In addition to typical fibrils abundantly found at the equilibrium phase, this analysis revealed the existence of a noticeable nonfibrillar fraction where α-synuclein was present …