Copper-driven Deselenization: Strategy for Selective Conversion of Copper Ion into Nanozyme
and Its possible Implication for Copper-Related Disorders

Ashish Chalana

Abstract

Copper-driven Deselenization: Strategy for Selective Conversion of Copper Ion into Nanozyme and Its possible Implication for Copper-Related Disorders

The copper (Cu), an essential trace element to humans,
is involved in numerous biological processes in our
body. However, the excess Cu is equally detrimental as
it produces hydroxyl radical (•OH) from H2O2 via Fenton-
type reactions, and thereby causes oxidative damage
to proteins, lipids, and nucleic acids. The intracellular
Cu concentration is, thus, strictly maintained by proteins
such as metallothioneines (MTs), ATP7A and ATP7B,
ATOX1 and CCS, and endogenous thiol, glutathione
(GSH). The majority of cytosolic Cu is bound to GSH,
the most abundant intracellular Cu binding ligand of low
molecular mass in living cells and is known to be a major
contributor to Cu exchangeable pool in the cytosol. Mutation
of ATP7B gene results non-functional of ATP7B protein
causing Cu over-load in tissues including liver, brain
of patients with Wilson’s disease (WD) and excess Cu has
been implicated in the progression of neurodegenerative
disorders including Alzheimer’s and Parkinson’s diseases.
Medical therapy in WD involves lifelong treatment
with Cu chelators (penicillamine, trientine) that bind
Cu directly in blood and tissues and facilitate its excretion.
4 However, chelation therapy is not always efficient
for symptomatic neurological patients and has harmful
side effects and, thus, efforts were made to discover tissue
specific chelators. Thus, there is an urgent need to
develop new synthetic molecules to cure the copper related
disorders. Here, we will discuss the discovery of new
synthetic molecule (1,3-bis(2-hydroxyethyl)-1H-benzoimidazole-
2-selenone) (1)5 which has remarkable ability to
reduce the bioavailability of intracellular Cu concentration
by removing Cu from glutathione, a major cytosolic
Cu-binding ligand, and thereafter converts it into copper
selenide nanozyme that exhibits remarkable glutathione
peroxidase (GPx)-like activity with an excellent cytoprotective
effect against oxidative stress in hepatocyte.