Predictive association of copper metabolism proteins with Alzheimer’s disease and Parkinson’s disease: a preliminary perspective Amit Pal • Ashok Kumar • Rajendra Prasad Received: 16 December 2013 / Accepted: 30 December 2013 / Published online: 17 January 2014 Ó Springer Science+Business Media New York 2014 Abstract Neurodegenerative diseases, Alzheimer’s disease (AD) and Parkinson’s disease (PD), constitute a major worldwide health problem. Several hypothesis have been put forth to elucidate the basis of onset and pathogenesis of AD and PD; however, till date, none of these seems to clearly elucidate the complex pathoet- iology of these disorders. Notably, copper dyshomeo- stasis has been shown to underlie the pathophysiology of several neurodegenerative diseases including AD and PD. Numerous studies have concluded beyond doubt that imbalance in copper homeostatic mecha- nisms in conjunction with aging causes an acceleration in the copper toxicity elicited oxidative stress, which is detrimental to the central nervous system. Amyloid precursor protein and a-synuclein protein involved in AD and PD are copper binding proteins, respectively. In this review, we have discussed the possible association of copper metabolism proteins with AD and PD along with briefly outlining the expanding proportion of ‘‘copper interactome’’ in human biology. Using net- work biology, we found that copper metabolism proteins, superoxide dismutase 1 and ceruloplasmin may represent direct and indirect link with AD and PD, respectively. Keywords Copper dyshomeostasis Á Wilson’s disease Á Alzheimer’s disease Á Parkinson’s disease Á Network biology Introduction Copper (Cu) is an essential micronutrient fundamental to human nutrition as evident by fatal Menke disease and Wilson’s disease (WD) caused due to copper deficiency and excess, respectively (Strausak et al. 2001). Owing to its redox active property, copper is imperative for several cuproenzymes/proteins (Supple- mentary material 1). Despite being essential, the excess of copper causes production of highly damaging free hydroxyl radicals via Fenton or Haber–Weiss type reactions resulting in oxidative stress and cytotoxicity. Oxidative stress causes cleavage of DNA, protein oxidation and lipid peroxidation, and central nervous system (CNS) is particularly susceptible to oxidative stress due to high levels of polyunsaturated lipids in neuronal membranes. Notably, oxidative stress has also been shown to induce cognitive deficits (Kucukatay et al. 2007; Lima et al. 2008; Rahman et al. 2009). Several studies have implicated imbalance in copper Electronic supplementary material The online version of this article (doi:10.1007/s10534-013-9702-7) contains supple- mentary material, which is available to authorized users. A. Pal Á R. Prasad (&) Department of Biochemistry, PGIMER, Chandigarh 160012, India e-mail: fateh1977@yahoo.com A. Kumar Department of System Biology and Bioinformatics, Panjab University, Chandigarh, India 123 Biometals (2014) 27:25–31 DOI 10.1007/s10534-013-9702-7