寡合物通过引起渐进式双端突触失调和突触损失来调节突触命运
bioRxiv : the preprint server for biology
|September 26, 2025
概括
寡聚物通过破坏前突触和后突触功能,导致渐进的突触恶化,导致持续的衰弱或完全的突触损失. 这项研究揭示了阿尔茨海默病发病过程中的事件序列.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 突触功能对认知至关重要,其丧失与阿尔茨海默病 (AD) 有关.
- 致病性寡合体在AD大脑中积累,急性损害突触可塑性并导致突触损失.
- 寡合体调节前突触和后突触区的确切机制尚不清楚.
研究的目的:
- 为了绘制图形后突触蛋白质组的动态变化,急性暴露在寡合物后.
- 确定陶寡合体对人体神经元前突触和后突触区的时间影响.
- 阐明导致突触功能障碍和恶化的病理生理事件的序列.
主要方法:
- 在人类诱导多能干细胞 (iPSC) 衍生神经元中开发了一种近距离标记工具 (APEX2-PSD-95).
- 映射了30分钟暴露于重组寡合体后的突触后蛋白质组变化.
- 利用免疫细胞化学,电生理学和电子显微镜来评估14天内的突触变化.
主要成果:
- 急性寡合体暴露导致了渐进的突触恶化,影响了突触前和突触后部位.
- 观察到立即下调的动因运动蛋白 (Myosin-Va,Myosin-10) 和受损的AMPA受体 (AMPAR) 贩运.
- 后突触部位的逐渐丧失 (PSD-95) 之前的突触前终端损失 (Synapsin),与持续的AMPAR下调和可塑性损害.
结论:
- 揭示了tau寡合体诱导的双端突触恶化中的一系列事件.
- 确定了两个突触命运:持续的功能衰弱或完全的突触损失.
- 提供了对阿尔茨海默病中突触功能障碍背后的分子机制的见解.
相关概念视频
Long-term Depression
3.1K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over...
Calcium Ion Concentration Mechanism
If over...
3.1K
Long-term Depression
33.1K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
33.1K
Long-term Potentiation
3.4K
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
Hebbian LTP
LTP can occur when...
Hebbian LTP
LTP can occur when...
3.4K
Long-term Potentiation
58.3K
Long-term potentiation, or LTP, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTP is the process of synaptic strengthening that occurs over time between pre- and postsynaptic neuronal connections. The synaptic strengthening of LTP works in opposition to the synaptic weakening of long-term depression (LTD) and together are the main mechanisms that underlie learning and memory.
58.3K
Neurotransmitters
2.6K
Neurotransmitters are essential chemical messengers within the nervous system, facilitating the communication between neurons. These chemical messengers, varying in function and effect, are critical for sustaining various aspects of neurological health and emotional well-being.
2.6K
Excitatory and Inhibitory Effects of Neurotransmitters
12.6K
When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
12.6K


