时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
Synaptic transmission is a sophisticated process wherein neurotransmitters released from synaptic vesicles (SVs) of presynaptic neuronal terminals bind to and activate receptors on postsynaptic neurons, subsequently leading to the activation of postsynaptic signals.；This process is tightly regulated to precision.
方法
During synaptic signaling, a finely tuned equilibrium between excitatory and inhibitory inputs is essential for sustaining physiological brain activity.；PICALM promotes amyloid plaque deposition by affecting Aβ metabolism, as shown in cell culture and APP/PS1 mice.；When iPSCs derived from C9orf72 patients, along with isogenic corrected controls, are differentiated into excitatory cortical neurons and then cocultured with primary mouse astrocytes, multielectrode array recordings show heightened burst firing frequency and impaired presynaptic vesicle dynamics, leading to defective synaptic transmission.
核心结论
Synapses act as core computational units that support higher cognitive functions in the brain.；Early defects in synaptic signaling and impairments in plasticity, induced by abnormal neuronal activity, are associated with AD, PD, HD, and ALS.；Mounting evidence suggests that soluble Aβ oligomers impair synaptic transmission and plasticity, leading to early synaptic failure prior to overt neurodegeneration in AD., Defects or impairments in pre- and postsynaptic mechanisms and synaptic plasticity are involved in the impairment of neural circuits in AD, a phenomenon documented in both mouse models and human patients, with a particular impact on the delicate balance between excitatory and inhibitory signaling. ‖ 结论：Given the multifactorial complexity of NDD pathophysiology, early glial‑synapse targeting may effectively complement current treatments.
局限
Although numerous neuropathological studies have examined alterations in GABA levels and function using postmortem tissue from AD patients, the results remain inconsistent due to heterogeneity and postmortem delays.；Ultimately, choline is taken back up into presynaptic neurons through the choline transporter (CHT1), which constitutes the rate‑limiting step in ACh synthesis, allowing ACh to be resynthesized.
对本项目的价值
★★☆☆☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。
全文来源
PMC JATS 全文（正文 143,242 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：Synaptic transmission and plasticity: molecular mechanisms, biological functions and therapeutic opportunities in neurodegenerative diseases.
- 期刊与标识：Signal Transduct Target Ther · PMID 42951886 · DOI 10.1038/s41392-026-02776-4
A 级证据分级：A 级（同行评议人体研究）
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