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.