Brady Emily B, McQuillan Molly, Medeiros Audrey T, Bubacco Luigi, Sousa Rui, Lafer Eileen M, Morgan Jennifer R
The Eugene Bell Center for Regenerative Biology and Tissue Engineering, Marine Biological Laboratory, Woods Hole, Massachusetts, United States.
Department of Biology, Duke University, Durham, North Carolina, United States.
MicroPubl Biol. 2023 Mar 1;2023. doi: 10.17912/micropub.biology.000737. eCollection 2023.
Aberrant buildup of α-synuclein is associated with Parkinson's disease (PD) and other neurodegenerative disorders. At synapses, α-synuclein accumulation leads to severe synaptic vesicle trafficking defects. We previously demonstrated that different molecular species of α-synuclein produce distinct effects on synaptic vesicle recycling, and that the synaptic phenotypes caused by monomeric α-synuclein were ameliorated by Hsc70. Here, we tested whether Hsc70 could also correct synaptic deficits induced by α-synuclein dimers. Indeed, co-injection of Hsc70 with α-synuclein dimers completely reversed the synaptic deficits, resulting in synapses with normal appearance. This work lends additional support for pursuing chaperone-based strategies to treat PD and other synucleinopathies.
α-突触核蛋白的异常聚集与帕金森病（PD）及其他神经退行性疾病相关。在突触处，α-突触核蛋白的积累会导致严重的突触小泡运输缺陷。我们之前证明，不同分子形式的α-突触核蛋白对突触小泡循环产生不同影响，并且单体α-突触核蛋白引起的突触表型可被热休克蛋白70（Hsc70）改善。在此，我们测试了Hsc70是否也能纠正由α-突触核蛋白二聚体诱导的突触缺陷。事实上，将Hsc70与α-突触核蛋白二聚体共同注射可完全逆转突触缺陷，使突触外观正常。这项工作为采用基于伴侣蛋白的策略治疗PD及其他突触核蛋白病提供了更多支持。
