Progress and Prospects in Parkinson's Research/Causes/Toxins/Copper

Background
Copper is a metallic element (symbol Cu) with an atomic number of 29.

It is an essential trace element in humans and the recommended adult daily intake is 0.97 mg/day It is  found in whole grain cereals, vegetables, oysters, offal (particularly liver), cherries, dark chocolate, fruits, leafy green vegetables, nuts, poultry, prunes, and soybeans products such as tofu.

Copper deficiency produces anaemia, bone marrow failure and ultimately a form of leukaemia.

If copper accumulates abnormally in the body it causes Wilson's Disease.  This produces the familiar symptoms of Parkinson's Disease - cogwheel rigidity, bradykinesia, lack of balance, hand tremor, masked facial expressions, slurred speech, ataxia (lack of coordination) or dystonia (twisting and repetitive movements of part of the body). Other symptoms are seizures and migraine and cognitive deficits. Wilson's Disease is generally characterised by distinctive rings around the iris of the eyes.

Research
1987

Pall et al and measured the copper concentrations in the cererbrospinal fluid of 24 PD patients and compared them with 39 controls. The PD patients had significantly higher levels of copper.

2007

Gibney describes a Polish study into the effects of raised copper levels on dopaminergic neurons.

"“To examine the precise role of copper in alpha-synuclein aggregation, the Polish team studied how copper(II) ions interact with fragments of a mutant form of alpha-synuclein that is particularly prone to aggregation. They found that the ions bind to the peptide fragments primarily through histidine, methionine and lysine residues. Copper binding makes these residues more susceptible to reaction"

2012

Rasia et al demonstrated that copper accelerated the aggregation of alpha synuclein, which is one of the pathological hallmarks of PD.

" By using numerous spectroscopic techniques (absorption, CD, EPR, and NMR), we have located the primary binding for Cu(II) to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry. "