Neurodegeneration from a medical point of view.
The role of metal ions in neurodegenerative diseases: a bioinorganic chemist view.
During the last decades the interest in metal ions in brain has gained a lot of attention. One of the main reasons was the observation that metal ions (mostly Fe, Cu, and Zn) seems to be involved in several neurodegenerative diseases (ND), as a mismetabolism of these metal ions in Alzheimer, Parkinson, Prion, amyloid lateral sclerosis etc. is well documented. It was recognized that metal-binding sites into key proteins involved in these diseases are crucial and metal binding molecules are of potential therapeutic interest.
In order to understand this in a broader sense, one has to considerer the peculiarities of the metal metabolism in the brain compared to most other tissues. Another key factor is the connection of the redox active metal ions, Fe and Cu, with the oxygen metabolism, as this is involved in the oxidative stress observed in these ND.
The lecture will give insights into the following questions:
– What is so special about the brain (compared to other tissues) that metal ions seem to have important impacts in a multitude of neuronal diseases?
– Why is the loss of control of metal ions metabolism (mismetabolism) a problem for the organism? Are the general features for the quite different ND?
– Why is in most of these NDs oxidative stress implicated? And why do have antioxidants like vitamin E have no effects as anti ND drugs?
– Aggregation of the key proteins involved in the ND is a common feature. Is there a link between this and oxidative stress?
– What about therapeutic strategies based on metal ions to combat NDs like AD?
Lecture and practice on stability constant calculation program.
Summer school in Bioinorganic Chemistry PG
The theme of this contribution is chemical equilibrium.
Exposition of the basic principles applied to protonation and metal-binding equilibria. Illustrations to include hemoglobin/O2, ATP protonation, chelation therapy, NMR contrast reagents …
- Experimental methods for data collection – potentiometric, spectrophotometric, calorimetric, NMR data
- Computer programs for obtaining equilibrium constants from experimental data
- Practical experience in using HySS to examine equilibrium speciation
Enrique Garcia Espana
Elzbieta Gumienna Kontecka
Metals in the brain.
Management of metals in bacterials.
NMR approaches to study protein-protein interactions (PPIs):
- Chemical shift perturbation mapping
- Changes in protein dynamics
- Distance and orientational restraints (including paramagnetic restraints)
Case examples involving heme proteins (cytochrome c and HasA)
NMR approaches to study large multimolecular assemblies and their interactions: relaxation interference, cross-correlated relaxation induced polarization transfer, heteronuclear detection. Basic principles and limitations of the various approaches.
Ferritin: assignment of a 480 kDa protein; use of paramagnetic approaches to draw iron pathways. Complementarity between NMR and X-ray for the characterization of weak protein-metal ion interactions.
Maria Antonietta Zoroddu