Small angle X-ray scattering analysis of Cu(2+)-induced oligomers of the Alzheimer's amyloid β peptide.

Research into causes of Alzheimer's disease and its treatment has produced a tantalising array of hypotheses about the role of transition metal dyshomeostasis, many of them on the interaction of these metals with the neurotoxic amyloid-β peptide (Aβ). Here, we have used small angle X-ray scattering (SAXS) to study the effect of the molar ratio, Cu(2+)/Aβ, on the early three-dimensional structures of the Aβ1-40 and Cu(2+)/Aβ1-42 peptides in solution. We found that at molar ratios of 0.

Sedimentation velocity analysis of amyloid fibrils.

Analytical ultracentrifugation is a classical technique used to study the solution behavior of proteins. Experimentally determined sedimentation coefficients provide information regarding the size, shape, and interactions of biological macromolecules. Sedimentation velocity methods have been used to characterize the different aggregation states of amyloid oligomers and fibrils.

Alpha-synuclein induced membrane depolarization and loss of phosphorylation capacity of isolated rat brain mitochondria: implications in Parkinson's disease.

This study demonstrates that in vitro incubation of isolated rat brain mitochondria with recombinant human alpha-synuclein leads to dose-dependent loss of mitochondrial transmembrane potential and phosphorylation capacity. However, alpha-synuclein does not seem to have any significant effect on the activities of respiratory chain complexes under similar conditions of incubation suggesting that the former may impair mitochondrial bioenergetics by direct effect on mitochondrial membranes. Moreover, the recombinant wild type alpha-synuclein and different mutant forms (A30P, A53T and E46K) have essentially similar effects on rat brain isolated mitochondria.

Modulation of alpha-synuclein aggregation by dopamine: a review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by (1) the selective loss of dopaminergic neurons in the substantia nigra and (2) the deposition of misfolded alpha-synuclein (alpha-syn) as amyloid fibrils in the intracellular Lewy bodies in various region of the brain. Current thinking suggests that an interaction between alpha-syn and dopamine (DA) leads to the selective death of neuronal cells and the accumulation of misfolded alpha-syn. However, the exact mechanism by which this occurs is not fully defined.