AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation

Dopaminergic neuronal loss is the main pathological character of Parkinson’s disease (PD). Abnormal tau hyperphosphorylation will lead to dopaminergic neuronal loss. An indazole derivative 6-amino-1-methyl-indazole (AMI) successfully synthesized to inhibit tau hyperphosphorylation may exert a neurop...

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Main Authors:	Zhang Mao, Zhu Wen-ting, Wang Hai-tao, Yu Hui, Lan Shi-yi, Xu Jiang-ping, Wang Wen-ya
Format:	Article
Language:	English
Published:	Frontiers Media S.A. 2020-11-01
Series:	Frontiers in Molecular Neuroscience
Subjects:	6-amino-1-methyl-indazole Parkinson’s disease tau SH-SY5Y MPTP
Online Access:	https://www.frontiersin.org/articles/10.3389/fnmol.2020.00165/full

id	doaj-d22e1c564f8641729cff173df3b564f8
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spelling	doaj-d22e1c564f8641729cff173df3b564f82020-11-25T04:10:34ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992020-11-011310.3389/fnmol.2020.00165510844AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau PhosphorylationZhang Mao0Zhu Wen-ting1Wang Hai-tao2Yu Hui3Lan Shi-yi4Xu Jiang-ping5Wang Wen-ya6School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaThe Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaSchool of Basic Medical Science, Southern Medical University, Guangzhou, China.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaDopaminergic neuronal loss is the main pathological character of Parkinson’s disease (PD). Abnormal tau hyperphosphorylation will lead to dopaminergic neuronal loss. An indazole derivative 6-amino-1-methyl-indazole (AMI) successfully synthesized to inhibit tau hyperphosphorylation may exert a neuroprotective effect. The in vitro study showed that AMI effectively increased cell viability and alleviated the apoptosis induced by MPP+ in SH-SY5Y cells. In addition, AMI treatment significantly decreased the expression of p-tau and upstream kinases GSK-3β. In the MPTP-induced PD mice models, we found AMI apparently preserved dopaminergic neurons in the substantia nigra and improved the PD behavioral symptoms. Our results demonstrate that AMI exerts a neuroprotective effect by inhibiting tau hyperphosphorylation, representing a promising new candidate for PD treatment.https://www.frontiersin.org/articles/10.3389/fnmol.2020.00165/full6-amino-1-methyl-indazoleParkinson’s diseasetauSH-SY5YMPTP
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Zhang Mao Zhu Wen-ting Wang Hai-tao Yu Hui Lan Shi-yi Xu Jiang-ping Wang Wen-ya
spellingShingle	Zhang Mao Zhu Wen-ting Wang Hai-tao Yu Hui Lan Shi-yi Xu Jiang-ping Wang Wen-ya AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation Frontiers in Molecular Neuroscience 6-amino-1-methyl-indazole Parkinson’s disease tau SH-SY5Y MPTP
author_facet	Zhang Mao Zhu Wen-ting Wang Hai-tao Yu Hui Lan Shi-yi Xu Jiang-ping Wang Wen-ya
author_sort	Zhang Mao
title	AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation
title_short	AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation
title_full	AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation
title_fullStr	AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation
title_full_unstemmed	AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation
title_sort	ami, an indazole derivative, improves parkinson’s disease by inhibiting tau phosphorylation
publisher	Frontiers Media S.A.
series	Frontiers in Molecular Neuroscience
issn	1662-5099
publishDate	2020-11-01
description	Dopaminergic neuronal loss is the main pathological character of Parkinson’s disease (PD). Abnormal tau hyperphosphorylation will lead to dopaminergic neuronal loss. An indazole derivative 6-amino-1-methyl-indazole (AMI) successfully synthesized to inhibit tau hyperphosphorylation may exert a neuroprotective effect. The in vitro study showed that AMI effectively increased cell viability and alleviated the apoptosis induced by MPP+ in SH-SY5Y cells. In addition, AMI treatment significantly decreased the expression of p-tau and upstream kinases GSK-3β. In the MPTP-induced PD mice models, we found AMI apparently preserved dopaminergic neurons in the substantia nigra and improved the PD behavioral symptoms. Our results demonstrate that AMI exerts a neuroprotective effect by inhibiting tau hyperphosphorylation, representing a promising new candidate for PD treatment.
topic	6-amino-1-methyl-indazole Parkinson’s disease tau SH-SY5Y MPTP
url	https://www.frontiersin.org/articles/10.3389/fnmol.2020.00165/full
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AMI, an Indazole Derivative, Improves Parkinson’s Disease by Inhibiting Tau Phosphorylation

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