Zinc-metallothionein: a potential mediator of antioxidant defence mechanisms in response to dopamine-induced stress.

Clinically, Parkinson's disease (PD) is a neurodegenerative disorder characterized by the development of tremors and rigidity that is found primarily in patients over the age of 50. At the cellular level, it is clear that the pathology of PD results from the progressive loss of dopaminergic neurons in the substantia nigra. Several lines of evidence have implicated oxidative stress as a contributing factor to the depletion of dopaminergic neurons in PD. Under conditions of oxidative stress, the neurotransmitter dopamine can be oxidized to form neurotoxic quinone and semiquinone products. While dopaquinones are known to be extremely reactive towards sulfhydryl groups of many cellular substrates, mounting evidence suggests that their toxic effects can be quenched by intrinsic antioxidant mechanisms (e.g., glutathione). However, to respond appropriately to differing levels of oxidative stress, cells require a mechanism to regulate an appropriate response. This manuscript proposes metallothionein as a major cellular sensor of oxidized dopamine stress and metallothionein-mediated Zn2+ mobilization as an effecter signal that is used by the cell to manage oxidized dopamine as an intrinsic neurotoxin.

The solution conformation of C-glycosyl analogues of the sialyl-Tn antigen.

The conformational behavior of two C-glycosyl analogues of the sialyl-Tn antigen has been determined by a combination of NMR methods and molecular mechanics calculations. Both compounds show a major solution conformation that is drastically different from the major one of the natural compound.