HSF1 inhibits microglia activation to attenuate neuroinflammation via regulating miR-214-3p and NFATc2 
in Parkinson’s disease

Yuangao Liao; Yong Gu; Jinhua Wang; Yu Tian; Xiaohong Ni; Lei Zhou; Ye Ye; Guangming Xia

doi:10.5114/fn.2022.122800

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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abstract:

Original paper

HSF1 inhibits microglia activation to attenuate neuroinflammation via regulating miR-214-3p and NFATc2 in Parkinson’s disease

Yuangao Liao

¹

,

Yong Gu

²

,

Jinhua Wang

¹

,

Yu Tian

¹

,

Xiaohong Ni

¹

,

Lei Zhou

¹

,

Ye Ye

¹

,

Guangming Xia

¹

Department of Neurology, Huanggang Central Hospital, Huanggang, Hubei, China
Clinical Research Center, Hainan Provincial Hospital of Chinese Medicine, Haikou, Hainan, China

Folia Neuropathol 2023; 61 (1): 53-67

DOI: https://doi.org/10.5114/fn.2022.122800

Online publish date: 2023/03/24

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Parkinson’s disease (PD) is characterized by microglia activation that leads to neuroinflammation. Heat shock transcription factor 1 (HSF1) is known to exert neuroprotective effects on neurodegenerative diseases. This study sought to analyse the role and mechanism of HSF1 in PD-induced neuroinflammation. The PD mouse models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animal behaviour capacities and neuronal damage were assessed via behavioural tests, tyrosine hydroxylase (TH) staining, and immunofluorescence. Levels of HSF1, miR-214-3p, nuclear factor of activated T cells 2 (NFATc2), and neuroinflammatory factors were detected via RT-qPCR, Western blotting, and ELISA.Binding relationships between HSF1 and miR-214-3p, miR-214-3p, and NFATc2 were tested via dual-luciferase or chromatin immunoprecipitation assays. Functional rescue experiments were designed to confirm the roles of miR-214-3p and NFATc2. HSF1 expression in brain tissues was downregulated upon MPTP treatment. HSF1 overexpression reduced motor deficits and loss of dopaminergic neurons, increased TH-positive neurons, and repressed neuroinflammation and micro-glia activation. Mechanically, HSF1 bound to the miR-214-3p promoter to increase its expression and inhibited NFATc2 transcription. miR-214-3p downregulation or NFATc2 overexpression reversed the inhibition of HSF1 overexpression on neuroinflammation and microglia activation. Overall, our findings unveiled the therapeutic role of HSF1 in PD-induced neuroinflammation and microglia activation via regulating miR-214-3p and NFATc2.

keywords:

HSF1 inhibits microglia activation to attenuate neuroinflammation via regulating miR-214-3p and NFATc2 in Parkinson’s disease

Yuangao Liao 1 , Yong Gu 2 , Jinhua Wang 1 , Yu Tian 1 , Xiaohong Ni 1 , Lei Zhou 1 , Ye Ye 1 , Guangming Xia 1

Parkinson’s disease, HSF1, microglia, neuroinflammation, miR-214-3p, NFATc2, transcription factor

Yuangao Liao

¹

,

Yong Gu

²

,

Jinhua Wang

¹

,

Yu Tian

¹

,

Xiaohong Ni

¹

,

Lei Zhou

¹

,

Ye Ye

¹

,

Guangming Xia

¹