Effects of α7 nicotinic acetylcholine receptor agonist against α-synuclein-induced neurotoxicity

被引：1
|
作者：
Takizawa, Shinnosuke [1 ]
Ohuchi, Kazuki [1 ]
Fujimaki, Ayaka [1 ]
Ito, Taisei [1 ]
Murakami, Takanori [1 ]
Kurita, Hisaka [1 ]
Inden, Masatoshi [1 ]
机构：
[1] Gifu Pharmaceut Univ, Lab Med Therapeut & Mol Therapeut, 1-25-4 Daigaku Nishi, Gifu, Gifu 5011196, Japan
来源：
NEUROSCIENCE LETTERS | 2024年 / 823卷
基金：
日本学术振兴会;
关键词：
alpha 7 nicotinic acetylcholine receptor; Neuroprotection; Autophagy; MEDIATED NEUROPROTECTION;
D O I：
10.1016/j.neulet.2024.137654
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
The alpha 7 neuronal nicotinic acetylcholine receptor (alpha 7 nAChR) is a potential target for the development of Parkinson's disease (PD) therapeutics. alpha-Synuclein (alpha-Syn), a principal component of Lewy bodies (cytoplasmic inclusions), is a major contributor to PD pathophysiology. Previous studies have demonstrated that activating alpha 7 nAChR protects against nigrostriatal dopamine degeneration in acute and chronic PD animal models induced by 6-hydroxydopamine and rotenone, respectively. In the present study, we investigated the effects of PNU282987, a selective alpha 7 nAChR agonist, against alpha-Syn-induced neurotoxicity in alpha-Syn(WT)-, alpha-Syn(A30P)-, and alpha-Syn(E46K)-N2a cells. PNU282987 exhibited substantial neuroprotection against both wild-type and mutant-type alpha-Syn-induced toxicity. Furthermore, PNU282987 promoted transcription factor EB activity and reduced intracellular alpha-Syn protein levels through autophagy induction. These results highlight the therapeutic potential of alpha 7 nAChR activation in diseases characterized by alpha-Syn aggregation, such as PD.
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页数：6
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