ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P57. Metal Ions and Oxidative Stress in Parkinson’s Disease
E. Gaggelli, D. Valensin and G. Valensin
Departmentof Chemistry, University of Siena, Via A.Moro 2, Siena 53100, Italy.
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, arising from the progressive
loss of dopaminergic neurons in the substantia nigra pars compacta.
In the surviving neurons, abnormal proteinaceous aggregates called Lewy bodies and Lewy neurites serve as
neuropathological hallmarks of the disease.
Point mutations in the a-synuclein (aS) gene cause rare forms of autosomaldominant familial PD, and wild-type
aS is the major component of the pathologic lesions characteristic of spontaneous PD.
aS is a 140 amino acid protein, which in solution adopts an ensemble of conformations that are stabilized by
long-range interactions and act to autoinhibit oligomerization and aggregation.
Reactive oxygen species are important in the pathogenesis of sporadic PD, since derangements in mitochondrial
complex I clearly lead to aggregation and accumulation of aS, and other forms of oxidative stress promote aS
aggregation.
A possible link between abnormal copper homoeostasis and the onset of PD was suggested on the basis that
copper(II) is the most effective metal ion in affecting selfoligomerization of aS.
With the aim of delineating the role of Cu(II) in chemical and biochemical properties of aS, preliminary data will
be herein presented that provide detailed structural delineation of the Cu(II) binding sites of aS.
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