ABSTRACT
Presenilin (PS) is the main pathogenic gene of familial Alzheimer's disease(AD). Mutations of PS gene can promote the processing of amyloid precursor protein (APP) into a toxic form of amyloid beta protein (Aβ), which plays an important role in the pathogenesis of AD.However, the current targeted therapy for Aβ has not yet produced a good effect on AD, suggesting the existence of additional pathogenic mechanisms.In recent years, the abnormal calcium homeostasis and its pathological role in AD have attracted people's attention.The calcium signaling pathway is regulated by presenilin.And the calcium regulation of PS gene mutant neurons is impaired, resulting in reduced ability to deal with oxidative stress, which leads to cell death and promotes the occurrence of AD.In addition, damage to neuronal autophagy induced by PS gene mutations also depends on the ability to partially deplete endoplasmic reticulum calcium content.Recent studies have shown that abnormal Ca 2+ homeostasis caused by PS gene mutations can lead to impaired mitochondrial metabolism and defects in brain network activity.This review will focus on the calcium signaling pathway, and explore the pathogenesis of presenilin in AD through the regulation of calcium signals from the perspectives of impaired autophagy, endoplasmic reticulum stress, mitochondrial dysfunction, apoptosis and defects in brain network activity, so as to provide ideas for the etiology of AD and the discovery of drug targets.
ABSTRACT
RESUMEN Los circuitos neuronales embrionarios poseen propiedades transitorias que originan una forma especial de actividad eléctrica conocida como Actividad Embrionaria Espontánea (AEE). La AEE se manifiesta tan pronto como las conexiones sinápticas se establecen, y consiste en descargas de potenciales de acción que ocurren sincrónicamente en la mayoría de las neuronas que componen el circuito, seguidas por largos periodos silentes en donde la excitabilidad se recupera paulatinamente para poder generar un nuevo episodio. Este tipo de actividad neuronal permite un alto grado de sincronización entre las neuronas de los circuitos en desarrollo y contribuye a la construcción y maduración sinápticas. Diversas regiones del sistema nervioso embrionario de los vertebrados presentan AEE ya que su manifestación depende de propiedades que comparten la mayoría de las redes neuronales en desarrollo: una conectividad intercelular redundante y el hecho de que el neurotransmisor ácido gamma-aminobutírico (GABA) es excitatorio durante el desarrollo embrionario (En el sistema nervioso adulto GABA es inhibitorio). En esta revisión discutimos la idea de que la presencia de AEE podría contribuir a establecer la fuerza sináptica de las sinapsis glutamatérgicas y GABAérgicas en un momento en el que ambas comparten una naturaleza excitadora, utilizando un mismo mecanismo de plasticidad sináptica conocido como plasticidad homeostática.
ABSTRACT Embrionic neural networks exibit a temporary special form of electrical activity known as Spontaneous Network Activity (SNA). SNA occurs as soon as synaptic conections are stablished and consists on synchronized action potential firing for most of the neurons on the network, followed by long silents periods where network excitability is gradually recovered till a new SNA episode can happen. This kind of neural activity allows a high level of synchronization among neurons on developing networks, contributing to synaptic connection and maturation. SNA has been described in several regions of the developing nervous system due to conserved properties among developing neural networks: redundant intercellular connectivity and the fact that the neurotransmitter gamma-aminobutiric acid (GABA) is excitatory during early embryonic development (GABA is inhibitory in the adult nervous system).In this review we discuss the hypothesis that SNA contributes to synaptic strenght for glutamatergic and gabaergic synapsis while both of them are excitatory, by using the same synaptic plasticity mechanism known as homeostatic plasticity.
ABSTRACT
Transcranial direct current stimulation (tDCS) is one of the brain stimulation techniques, which considered as an alternative treatment for Alzheimer's disease (AD). In AD, cognitive, behavior, and functional deteriorations are the result of synaptic dysfunction, neural circuit destabilization, and disrupted network activity, which are mainly caused by amyloid and tau deposition. tDCS modified neuronal resting membrane potential, synaptic plasticity, cortical neurotransmitters, astrocytes, cerebral blood flow, and functional connectivity, which could restore cognitive impairment. However, several small clinical studies that have been conducted so far have produced inconsistent results in patients with AD. Therefore, more systematic clinical studies are needed in the future.