From synaptic dynamics to cognitive decline: Molecular insights into neuroplasticity

Neuroplasticity, the nervous system's ability to adapt its activity in response to internal and external stimuli. This adaptability depends on activity-dependent mechanisms that alter the strength and efficiency of synaptic transmission. The key processes include neurotransmitter release, calcium ion influx, magnesium ion removal from N-methyl-d-aspartate (NMDA) receptors, trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, and complex intracellular signaling pathways. Glial cells and autophagic processes further contribute to the maintenance and regulation of synaptic plasticity. These mechanisms are pivotal for stabilizing synaptic connections and mitigating memory loss in neurological conditions such as Alzheimer's disease (AD). At the molecular level, synaptic plasticity involves an intricate network of proteins, receptors, and post-translational modifications that interact within coordinated signaling pathways to ensure structural and functional stability. Thus, any disruption in these mechanisms significantly contributes to the pathogenesis of various neurological disorders, including schizophrenia, depression, AD, and dementia. In this review, we explore the key molecular pathways that contribute to synaptic plasticity, ultimately aiming to understand disease pathology and related key targets for therapeutic interventions and disease prevention.