Researchers from the Post Graduate Institute of Medical Education and Research have identified possible involvement of copper metabolism proteins in sporadic Alzheimer’s disease (AD) and Parkinson’s disease (PD).
Prof Rajendra Prasad, head of department biochemistry said, “Copper is an important element which helps in the development of the central nervous system. However, it is a trace element which should be present in the body, under a limit. Its deficiency and abundance both can have adverse effect.” The pathoetiology of these neurodegenerative diseases, constituting a major worldwide health problem in the elderly, has not yet been clearly explained. Copper is an indispensable trace element for human nutrition, especially for the development and functioning of the central nervous system. Conspicuously, excess copper as well as its deficiency has been implicated in the pathophysiology of such neurodegenerative diseases.
Aberrations in copper homeostatic mechanisms together with aging causes an acceleration in the copper toxicity mediated oxidative stress, which is harmful to the central nervous system functioning. Notably, amyloid precursor protein (APP) and alpha-synuclein proteins implicated in AD and PD respectively are copper binding proteins.
Novel components of copper homeostasis in humans have been identified recently which have been characterised at the molecular level. These include copper-transporting P-type ATPases, Menkes and Wilson proteins, and copper chaperones. These findings have paved the way towards better understanding of the role of copper deficiency or copper toxicity in physiological and pathological conditions.
To identify the role of copper metabolism proteins in AD and PD, the researchers first constructed the ‘copper interactome’ with the help of network biology using ceruloplasmin and a set of proteins directly involved in human copper metabolism. They then merged the ‘copper interactome’ with three proteins involved in AD and two causing PD in humans. The researchers found that copper metabolism proteins, superoxide dismutase 1 and ceruloplasmin may represent direct and indirect linkage with AD and PD, respectively.
The study raises the prospect of finding connections between the ‘copper status’ and the AD and PD by means of the ‘copper interactome’, says lead researcher Prof Rajendra Prasad. The study has been cited in the ‘Nature’, an international medical journal. Dr Amit Pal, who has been part of this research, says it provides new insights on the role of metals, especially copper, in AD and PD and recognises novel therapy targets for multifactorial neurodegenerative diseases.