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.

引用

页数：6

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