Synapses allow for information exchange within the nervous system and are involved in neuronal circuitry formation and plasticity, resulting from neurons’ interactions and cooperation. The correct functioning of these structures is fundamental for learning and memory formation, during development, adulthood, and aging.
The physiological process of formation and elimination of synapses continues through the life span via synaptogenesis and synaptic pruning and a critical equilibrium between the two processes is essential for the correct development of cortical layers. Equilibrium instabilities may contribute to compromise or alter synaptic functions.
The impact of compromised synaptic activity is massive. In some cases, it leads to increased synapse pruning, synaptic density decrease, and severe circuitry rewiring, due to excessive synaptic elimination.
The main structural domain of the postsynaptic compartment is the so-called post-synaptic density (PSD). The PSD consists of a lattice-like array of interacting proteins organizing and stabilizing the postsynaptic structure within synapses. PSD proteins are enriched in PDZ domains supporting proteins’ interaction, taking part in trafficking, anchoring, and clustering receptors at the membrane level, regulating the dynamics of cytoskeletal structures.
Several studies have stressed the importance of the PSD in physiological and pathological states.
Fundamental PSD proteins are postsynaptic density protein-95 (PSD-95), Shank proteins, glutamate receptors complex, synaptic cell-adhesion proteins, Kalirin, Neuroligin, and various regulatory enzymes, as they play an important role in synaptic regulatory functions. Among many PSD member proteins, some are yet to be functionally studied.
Mutation of different PSD proteins is linked to various neurological disorders and synaptic failure can ultimately be linked to cognitive impairments, associated with neuropsychiatric or neurological disorders, including schizophrenia, autism spectrum disorders, depression, Parkinson's, and Alzheimer's disease.
For instance, several PSD proteins mutations have been linked to the pathophysiology of autism spectrum disorders: Shank2 mutation (loss-of-function) and Neuroligin (a cell adhesion molecule binding to presynaptic Neurexin) mutations. Though the exact mechanism of Neuroligins’ mutation association with Autism is not clear, we know it affects AMPA receptors signaling pathways.
Moreover, post-translational modifications such as palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation of PSD proteins, especially PSD-95, play a crucial role in synaptic stability, highlighting the important role of post-translational modifications in synaptic physiology and pathology.
This Research Topic aims to provide further insights on the synaptic pathological mechanisms contributing to various neurological disorders, focusing on the PSD.
To address this question, we welcome articles focusing on:
? Molecular mechanisms causing synaptic impairment – dendritic spine density anomalies and alterations, evidence from in vitro and in vivo studies at different time points (development, adulthood, aging) and in different experimental models
? Level of impact of synaptic failure leading to circuit impairment – evidence from affected circuits tightly connected to cognitive abilities
? Excessive synaptic elimination and its involvement in well-defined neurological diseases, hallmarked by cognitive impairment and decline.
? Post-translational modifications at PSD level – balance between stability and plasticity
? Pharmacological enhancement of learning and memory via synapses/circuitry targeting in experimental animal models
? Neuroprotective therapeutic approaches targeting synapses and potentially enhancing or rescuing synaptic function
Synapses allow for information exchange within the nervous system and are involved in neuronal circuitry formation and plasticity, resulting from neurons’ interactions and cooperation. The correct functioning of these structures is fundamental for learning and memory formation, during development, adulthood, and aging.
The physiological process of formation and elimination of synapses continues through the life span via synaptogenesis and synaptic pruning and a critical equilibrium between the two processes is essential for the correct development of cortical layers. Equilibrium instabilities may contribute to compromise or alter synaptic functions.
The impact of compromised synaptic activity is massive. In some cases, it leads to increased synapse pruning, synaptic density decrease, and severe circuitry rewiring, due to excessive synaptic elimination.
The main structural domain of the postsynaptic compartment is the so-called post-synaptic density (PSD). The PSD consists of a lattice-like array of interacting proteins organizing and stabilizing the postsynaptic structure within synapses. PSD proteins are enriched in PDZ domains supporting proteins’ interaction, taking part in trafficking, anchoring, and clustering receptors at the membrane level, regulating the dynamics of cytoskeletal structures.
Several studies have stressed the importance of the PSD in physiological and pathological states.
Fundamental PSD proteins are postsynaptic density protein-95 (PSD-95), Shank proteins, glutamate receptors complex, synaptic cell-adhesion proteins, Kalirin, Neuroligin, and various regulatory enzymes, as they play an important role in synaptic regulatory functions. Among many PSD member proteins, some are yet to be functionally studied.
Mutation of different PSD proteins is linked to various neurological disorders and synaptic failure can ultimately be linked to cognitive impairments, associated with neuropsychiatric or neurological disorders, including schizophrenia, autism spectrum disorders, depression, Parkinson's, and Alzheimer's disease.
For instance, several PSD proteins mutations have been linked to the pathophysiology of autism spectrum disorders: Shank2 mutation (loss-of-function) and Neuroligin (a cell adhesion molecule binding to presynaptic Neurexin) mutations. Though the exact mechanism of Neuroligins’ mutation association with Autism is not clear, we know it affects AMPA receptors signaling pathways.
Moreover, post-translational modifications such as palmitoylation, phosphorylation, ubiquitination, nitrosylation, and neddylation of PSD proteins, especially PSD-95, play a crucial role in synaptic stability, highlighting the important role of post-translational modifications in synaptic physiology and pathology.
This Research Topic aims to provide further insights on the synaptic pathological mechanisms contributing to various neurological disorders, focusing on the PSD.
To address this question, we welcome articles focusing on:
? Molecular mechanisms causing synaptic impairment – dendritic spine density anomalies and alterations, evidence from in vitro and in vivo studies at different time points (development, adulthood, aging) and in different experimental models
? Level of impact of synaptic failure leading to circuit impairment – evidence from affected circuits tightly connected to cognitive abilities
? Excessive synaptic elimination and its involvement in well-defined neurological diseases, hallmarked by cognitive impairment and decline.
? Post-translational modifications at PSD level – balance between stability and plasticity
? Pharmacological enhancement of learning and memory via synapses/circuitry targeting in experimental animal models
? Neuroprotective therapeutic approaches targeting synapses and potentially enhancing or rescuing synaptic function