Copper and Copper Proteins in Parkinson’s Disease

Abstract

Copper is a transition metal that has been linked to pathological and beneficial effects in neurodegenerative diseases. In Parkinson's disease, free copper is related to increased oxidative stress, alpha-synuclein oligomerization, and Lewy body formation. Decreased copper along with increased iron has been found in substantia nigra and caudate nucleus of Parkinson's disease patients. Copper influences iron content in the brain through ferroxidase ceruloplasmin activity; therefore decreased protein-bound copper in brain may enhance iron accumulation and the associated oxidative stress. The function of other copper-binding proteins such as Cu/Zn-SOD and metallothioneins is also beneficial to prevent neurodegeneration. Copper may regulate neurotransmission since it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA A receptors. Some of the proteins involved in copper transport are the transporters CTR1, ATP7A, and ATP7B and the chaperone ATOX1. There is limited information about the role of those biomolecules in the pathophysiology of Parkinson's disease; for instance, it is known that CTR1 is decreased in substantia nigra pars compacta in Parkinson's disease and that a mutation in ATP7B could be associated with Parkinson's disease. Regarding copper-related therapies, copper supplementation can represent a plausible alternative, while copper chelation may even aggravate the pathology.

Metallothionein, Copper and Alpha-Synuclein in Alpha-Synucleinopathies

“…Indeed, the point mutation H50Q which leads to a familial form of PD corresponds to the major copper(II) binding site (Proukakis et al, 2013) and binding of copper(II) to this mutant results in a structurally different species compared to the copper-WT species (Villar-Piqué et al, 2016). The ability of copper to accept or donate electrons implicates it in the production of ROS in PD (Barnham et al, 2004; Barnham and Bush, 2008; Valensin et al, 2016), and it has more recently been shown that in the SN, total tissue copper is decreased (Montes et al, 2014). Moreover, some studies have found an increase of serum copper, and indeed a positive correlation between high concentration levels and severity of the disease (Brewer, 2009; Arnal et al, 2010).…”

Redox-implications associated with the formation of complexes between copper ions and reduced or oxidized glutathione

“…These oxidative events are generally regarded as crucial, as they can lead to cell death and/or to the development of copperrelated diseases, such as Indian child cirrhosis and Wilson disease, in which a strong association between intra-hepatic copper levels and massive oxidative injury (especially within its mitochondria) has been well established [22]. Copper excess is also associated with certain forms of cancer, cardiomyopathies, Alzheimer's and Parkinson's disease [23,24].…”

Micronutrients and their diverse role in agricultural crops: advances and future prospective

“…Plastocyanin, being the most abundant copper protein promotes electron transport in the thylakoid lumen of chloroplasts (Yruela 2005; Abdel- (2000), Dear and Weir (2004) Boron-toxicity Above 0.3-1 ppm and 3-100 lg g -1 dry weight Higher concentration of boron in plants would lead to Yellowing of the leaf tips and distorted shoot growth Chlorotic and necrotic patches in the margin/ older leaves spots on fruits Nable et al (1997), Stangoulis and Reid (2002), Reid et al (2004), Nable et al (1997) DW Improper growth rate and distortion or whitening (chlorosis) of young leaves Decrease in cell wall formation lignification in several tissues and curling of leaf margins Damages apical meristem, fruit formation, pollen development, the fruit and seed production, wood production Inhibits embryo development, seed viability and plant development Marschner (1995), Epstein and Bloom (2005), Ruiter (1969), Küpper et al (2003), Yruela (2005), Burkhead et al (2009a, b) Toxicity of Cu Above 20 lg g -1 DW or higher Chlorosis and necrosis, stunting, and inhibition of root and shoot growth Inhibit enzyme activity and protein function, which later produces highly toxic hydroxyl radicals leading to oxidative damage of plant cell Gratão et al (2005), Vinit-Dunand et al (2002), Küpper et al (2003), Yruela et al (2009) Ghany and Pilon 2008). Apart from this, some copper proteins that are localized in cytoplasm, stroma of chloroplast, peroxisomes and other plant organelles act as the most effective scavenger of reactive oxygen species (Yamasaki et al 2008;Montes et al 2014). Furthermore, Rehm and Schmitt (2002) suggested the unique role of Cu in optimal seed production and chlorophyll formation...…”