RESUMEN
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.
Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Plomo , Enfermedades Neurodegenerativas , Humanos , Plomo/toxicidad , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/inducido químicamente , Animales , Transducción de Señal/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacosRESUMEN
Lead (Pb2+) is a hazardous heavy metal that is pervasive in the human environment as a result of anthropogenic activity, and poses serious health risks, particularly in children. Due to its innumerable unique physical and chemical properties, it has various applications; therefore, it has become a common environmental pollutant. Lead may cause oxidative stress, and accumulating evidence indicates that oxidative stress influences the pathophysiology of lead poisoning, also called plumbism. The immune system is continually exposed to various environmental pathogens and xenobiotics, including heavy metals such as lead, and appears to be one of the most vulnerable targets. After being exposed to lead, cells are subjected to oxidative stress as a result of reactive oxygen species (ROS) production. When the generation and consumption of ROS are out of equilibrium, various cell structures, particularly phospholipids are disrupted leading to lipid peroxidation. Various inflammatory signalling pathways are activated as a consequence, along with reduced disease resistance, inflammation, autoimmunity, sensitization and disruption of the cell-mediated and humoral immune systems. Lead negatively affects the metabolism of cytokines, including the interleukins IL-2, IL-1b, IL-6, IL-4, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN), as well as the expression and functioning of inflammatory enzymes such as cyclooxygenases. However, the cause of toxicity depends on the kind of lead, dosage, route of entry, exposure period, age, host and genetic predisposition.