Influence of lead on cAMP-response element binding protein (CREB) and its implications in neurodegenerative disorders

Lead (Pb²⁺) is one of the most common toxic metals present in the environment, and lead exposure causes serious health issues in humans. Lead is widely used because of its physio-chemical characteristics, which include softness, corrosion resistance, ductility, and low conductivity. Lead affects almost all human organs, specifically the central nervous system. Lead neurotoxicity is connected to various neural pathways, including brain-derived neurotrophic factor (BDNF) protein level alterations, cyclic adenosine 3′,5′-monophosphate (cAMP) response element binding protein (CREB) pathway changes, and N-methyl-D-aspartate receptors (NMDARs) changes. Lead primarily affects protein kinase C (PKC) through the replacement of calcium (Ca²⁺) ions in the CREB pathway. In this review, we have discussed the effect of lead on the CREB pathway and its implications on the nervous system, highlighting its effects on learning, synaptic plasticity, memory, and cognitive deficits. This review provides an understanding of the lead-induced alterations in the CREB pathway, which can lead to the future prospect of its use as a diagnostic marker as well as a therapeutic target for neurodegenerative disorders.