Synaptic transmission and plasticity: molecular mechanisms, biological functions and therapeutic opportunities in neurodegenerative diseases.
9 affiliations
- 1Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
- 2Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
- 3University of Chinese Academy of Sciences, Beijing, China.
- 4Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
- 5Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [email protected].
- 6University of Chinese Academy of Sciences, Beijing, China. [email protected].
- 7Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [email protected].
- 8Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China. [email protected].
- 9University of Chinese Academy of Sciences, Beijing, China. [email protected].
Abstract
Synaptic transmission impairment and neuronal loss are hallmarks of neurodegenerative diseases (NDDs). To date, the absence of effective therapies for treating or preventing NDDs underscores the critical need to comprehend the mechanisms underlying synaptic loss and impairment to develop novel interventions. Synaptic transmission is a complex communication process between presynaptic and postsynaptic neurons. Separate postsynaptic receptors activated by a variety of neurotransmitters initiate different downstream signaling cascades that are modulated by receptor-associated auxiliary subunits. Moreover, glia-neuron interactions and various neuropeptides can also modulate diverse synaptic functions. In this review, we first summarize the presynaptic and postsynaptic regulatory mechanisms of synaptic transmission in glutamatergic, GABAergic, cholinergic, and dopaminergic neurons in NDDs. We then emphasize the fundamental role of microglia and astrocytes in maintaining neuronal homeostasis and discuss how glia-neuron cross-talk affects synaptic and neuronal function throughout the pathological processes of NDDs, as well as how aging accelerates synaptic dysfunction in NDDs. We also highlight therapeutic strategies aimed at preserving or restoring synaptic integrity, including approaches that enhance plasticity, fine‑tune neurotransmitter signaling, or target immune pathways. Finally, we evaluate the current state of research for each intervention class and consider the major obstacles and opportunities that lie ahead in developing effective synapse‑directed therapies for NDDs.
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BibTeX
@article{sun2026synaptic,
title = {{Synaptic transmission and plasticity: molecular mechanisms, biological functions and therapeutic opportunities in neurodegenerative diseases.}},
author = {Jianxu Sun and Ge Gao and Sitong Wang and Shuai Li and Jinglan Tang and Hongmei Liu and Tie-Shan Tang},
journal = {Signal transduction and targeted therapy},
year = {2026},
month = oct,
doi = {10.1038/s41392-026-02776-4},
url = {https://europepmc.org/article/MED/42951886},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Synaptic transmission and plasticity: molecular mechanisms, biological functions and therapeutic opportunities in neurodegenerative diseases.
AU - Jianxu Sun
AU - Ge Gao
AU - Sitong Wang
AU - Shuai Li
AU - Jinglan Tang
AU - Hongmei Liu
AU - Tie-Shan Tang
PY - 2026
DA - 2026/10/29
JO - Signal transduction and targeted therapy
DO - 10.1038/s41392-026-02776-4
UR - https://europepmc.org/article/MED/42951886
AB - Synaptic transmission impairment and neuronal loss are hallmarks of neurodegenerative diseases (NDDs). To date, the absence of effective therapies for treating or preventing NDDs underscores the critical need to comprehend the mechanisms underlying synaptic loss and impairment to develop novel interventions. Synaptic transmission is a complex communication process between presynaptic and postsynaptic neurons. Separate postsynaptic receptors activated by a variety of neurotransmitters initiate different downstream signaling cascades that are modulated by receptor-associated auxiliary subunits. Moreover, glia-neuron interactions and various neuropeptides can also modulate diverse synaptic functions. In this review, we first summarize the presynaptic and postsynaptic regulatory mechanisms of synaptic transmission in glutamatergic, GABAergic, cholinergic, and dopaminergic neurons in NDDs. We then emphasize the fundamental role of microglia and astrocytes in maintaining neuronal homeostasis and discuss how glia-neuron cross-talk affects synaptic and neuronal function throughout the pathological processes of NDDs, as well as how aging accelerates synaptic dysfunction in NDDs. We also highlight therapeutic strategies aimed at preserving or restoring synaptic integrity, including approaches that enhance plasticity, fine‑tune neurotransmitter signaling, or target immune pathways. Finally, we evaluate the current state of research for each intervention class and consider the major obstacles and opportunities that lie ahead in developing effective synapse‑directed therapies for NDDs.
SN - 2095-9907
SN - 2059-3635
ER -