Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Parkinson Disease: HELP
Articles by Ling-Ling Lu
Based on 13 articles published since 2010
(Why 13 articles?)
||||

Between 2010 and 2020, Lingli Lu wrote the following 13 articles about Parkinson Disease.
 
+ Citations + Abstracts
1 Review [Nurr1 and its potential use in diagnosis and gene therapy for PD]. 2010

Yang, Shuang / Lu, Ling-Ling / Yang, Hui. · ·Sheng Li Ke Xue Jin Zhan · Pubmed #21416982.

ABSTRACT: -- No abstract --

2 Article Galectin-1 attenuates neurodegeneration in Parkinson's disease model by modulating microglial MAPK/IκB/NFκB axis through its carbohydrate-recognition domain. 2020

Li, Yi / Chen, Ning / Wu, Chao / Lu, Yongquan / Gao, Ge / Duan, Chunli / Yang, Hui / Lu, Lingling. ·Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100069, China. · Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Nansihuanxilu 119, Fengtai District, Beijing 100070, China. · Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing 100069, China. Electronic address: lllu@ccmu.edu.cn. ·Brain Behav Immun · Pubmed #31669519.

ABSTRACT: The vicious cycle between the chronicactivationofmicroglia and dopamine neurons degeneration is linked with the progression of Parkinson's disease (PD). Targeting microglialactivationhas proven to be a viable option to develop a disease-modified therapy for PD. Galectin-1, which has been reported to have an anti-neuroinflammation effect was used in the present study to evaluate its therapeutic effects on microglia activation and neuronal degeneration in Parkinson's disease model. It was found that galectin-1 attenuated the inflammatory insult and the apoptosis of SK-N-SH human neuroblastoma cells from conditioned medium of activated microglia induced by Lipopolysaccharides (LPS). Nonetheless, galectin-1 administration (0.5 mg/kg) inhibited the microglia activation, improved the motor deficits in PD mice model induced by MPTP (25 mg/kg weight of mouse, i.p.) and prevented the degeneration of dopaminergic neurons in the substantia nigra. Administration of galectin-1 resulted in p38 and ERK1/2 dephosphorylation followed by IκB/NFκB signaling pathway inhibition. Galectin-1 significantly decreased the secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The protective effects and modulation of the MAPK/IκB/NFκB signaling pathway were abolished with β-D-galactose which blocked the carbohydrate-recognition domain of galectin-1. The present study demonstrated that galectin-1 inhibited microglia activation and ameliorated neurodegenerative process in PD model by modulating MAPK/IκB/NFκB axis through its carbohydrate-recognition domain.

3 Article Leucine Carboxyl Methyltransferase Downregulation and Protein Phosphatase Methylesterase Upregulation Contribute Toward the Inhibition of Protein Phosphatase 2A by α-Synuclein. 2018

Tian, Hao / Lu, Yongquan / Liu, Jia / Liu, Weijin / Lu, Lingling / Duan, Chunli / Gao, Ge / Yang, Hui. ·Department of Neurobiology Capital Medical University, Center of Parkinson's Disease Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Center of Neural Regeneration and Repair, Beijing, China. ·Front Aging Neurosci · Pubmed #29950985.

ABSTRACT: The pathology of Parkinson's disease (PD) is characterized by intracellular neurofibrillary tangles of phosphorylated α-synuclein (α-syn). Protein phosphatase 2A (PP2A) is responsible for α-syn dephosphorylation. Previous work has demonstrated that α-syn can regulate PP2A activity. However, the mechanisms underlying α-syn regulation of PP2A activity are not well understood. In this study, we found that α-syn overexpression induced increased α-syn phosphorylation at serine 129 (Ser129), and PP2A inhibition,

4 Article Simvastatin Inhibits Activation of NADPH Oxidase/p38 MAPK Pathway and Enhances Expression of Antioxidant Protein in Parkinson Disease Models. 2018

Tong, Huichun / Zhang, Xiuping / Meng, Xingjun / Lu, Lingli / Mai, Dongmei / Qu, Shaogang. ·Clinical Medicine Research Center, Shunde Hospital, Southern Medical University, Foshan, China. · Teaching Center of Experimental Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China. ·Front Mol Neurosci · Pubmed #29872377.

ABSTRACT: Evidence suggests that oxidative stress is involved in the pathogenesis of Parkinson disease (PD). Simvastatin has been suggested to protect against oxidative stress in several diseases. However, the molecular mechanisms by which simvastatin protects against neuropathology and oxidative damage in PD are poorly elucidated. In this study, we aimed to investigate the potential neuroprotective effects of simvastatin owing to its anti-oxidative properties in 6-hydroxydopamine (6-OHDA)-treated SH-SY5Y cells and mice. The results of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence and CCK-8 assay demonstrated that simvastatin reduced intracellular reactive oxygen species (ROS) levels and reversed apoptosis in 6-OHDA-treated SH-SY5Y cells. Mechanistic studies revealed that 6-OHDA-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase/p38 mitogen-activated protein kinase (MAPK) pathway was inhibited and nuclear factor-κB (NF-κB) nuclear transcription decreased in SH-SY5Y cells after simvastatin treatment. Enhanced expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and glutamate-cysteine ligase modifier subunit (GCLM) were observed after simvastatin treatment in 6-OHDA-treated SH-SY5Y cells.

5 Article Piperlongumine restores the balance of autophagy and apoptosis by increasing BCL2 phosphorylation in rotenone-induced Parkinson disease models. 2018

Liu, Jia / Liu, Weijin / Lu, Yongquan / Tian, Hao / Duan, Chunli / Lu, Lingling / Gao, Ge / Wu, Xia / Wang, Xiaomin / Yang, Hui. ·a Center of Parkinson Disease Beijing Institute for Brain Disorders, Beijing Key Laboratory on Parkinson Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing Center of Neural Regeneration and Repair, Department of Neurobiology, Capital Medical University , Beijing , China. · b School of Traditional Chinese Medicine , Capital Medical University , Beijing , China. ·Autophagy · Pubmed #29433359.

ABSTRACT: Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease and is caused by genetics, environmental factors and aging, with few treatments currently available. Apoptosis and macroautophagy/autophagy play critical roles in PD pathogenesis; as such, modulating their balance is a potential treatment strategy. BCL2 (B cell leukemia/lymphoma 2) is a key molecule regulating this balance. Piperlongumine (PLG) is an alkaloid extracted from Piper longum L. that has antiinflammatory and anticancer effects. The present study investigated the protective effects of PLG in rotenone-induced PD cell and mouse models. We found that PLG administration (2 and 4 mg/kg) for 4 wk attenuated motor deficits in mice and prevented the loss of dopaminergic neurons in the substantia nigra induced by oral administration of rotenone (10 mg/kg) for 6 wk. PLG improved cell viability and enhanced mitochondrial function in primary neurons and SK-N-SH cells. These protective effects were exerted via inhibition of apoptosis and induction of autophagy through enhancement of BCL2 phosphorylation at Ser70. These results demonstrate that PLG exerts therapeutic effects in a rotenone-induced PD models by restoring the balance between apoptosis and autophagy. ABBREVIATIONS: 6-OHDA, 6-hydroxydopamine; ACTB, actin, beta; BafA1, bafilomycin A

6 Article PINK1 suppresses alpha-synuclein-induced neuronal injury: a novel mechanism in protein phosphatase 2A activation. 2018

Yang, Weiwei / Wang, Xue / Liu, Jia / Duan, Chunli / Gao, Ge / Lu, Lingling / Yu, Shun / Yang, Hui. ·Department of Neurobiology, Center for Parkinson's Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Capital Medical University, Beijing, China. · Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China. ·Oncotarget · Pubmed #29416594.

ABSTRACT: Alpha-synuclein (α-Syn) and phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced putative kinase (PINK) 1 are proteins found in Lewy bodies, which are a pathological hallmark of Parkinson's disease (PD). PINK1 overexpression suppresses α-Syn-induced phenotypes and increases lifespan and health in an animal model of PD. It has been suggested that the two proteins regulate protein phosphatase (PP) 2A activity, but the underlying mechanisms and neuroprotective action of PP2A against PD-associated pathology are unknown. We found that α-Syn overexpression in SK-N-SH neuroblastoma cells and primary cortical neurons caused mitochondrial dysfunction and cell injury

7 Article Morphological analysis of mitochondria for evaluating the toxicity of α-synuclein in transgenic mice and isolated preparations by atomic force microscopy. 2017

Gao, Ge / Wang, Zhipeng / Lu, Lingling / Duan, Chunli / Wang, Xiaomin / Yang, Hui. ·Department of Neurobiology, Capital Medical University, Center of Parkinson Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, 100069, China. Electronic address: gaog@ccmu.edu.cn. · Department of Neurobiology, Capital Medical University, Center of Parkinson Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, 100069, China. Electronic address: 18600116009@163.com. · Department of Neurobiology, Capital Medical University, Center of Parkinson Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, 100069, China. Electronic address: lllu@ccmu.edu.cn. · Department of Neurobiology, Capital Medical University, Center of Parkinson Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, 100069, China. Electronic address: cldduan@ccmu.edu.cn. · Department of Neurobiology, Capital Medical University, Center of Parkinson Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, 100069, China. Electronic address: xmwang@ccmu.edu.cn. · Department of Neurobiology, Capital Medical University, Center of Parkinson Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing, 100069, China. Electronic address: Huiyang@ccmu.edu.cn. ·Biomed Pharmacother · Pubmed #29169728.

ABSTRACT: A key molecular event in the pathogenesis of Parkinson's disease is mitochondrial damage caused by α-synuclein (α-syn). Mitochondria mediates both necrosis and apoptosis, which are associated with morphological changes. However, the mechanism by which α-syn alters mitochondrial morphology remains unclear. To address this issue, we investigated mitochondrial permeability transition pore (mPTP) opening and changes in cardiolipin (CL) levels in mitochondria isolated from the brain of Thy1α-syn mice. Cytoplasmic cytochrome C and cleaved caspase-3 protein levels were upregulated in the brain of transgenic mice. Morphological analysis by atomic force microscopy (AFM) suggested a correlation between mitochondrial morphology and function in these animals. Incubation of isolated mitochondria with recombinant human α-synuclein N terminus (α-syn/N) decreased mitochondrial CL content. An AFM analysis showed that α-syn/N induced mitochondrial swelling and the formation of pore-like structures, which was associated with decreased mitochondrial transmembrane potential and complex I activity. The observed mitochondrial dysfunction was abrogated by treatment with the mPTP inhibitor cyclosporin A, although there was no recovery of CL content. These results provide insight into the mechanism by which α-syn/N directly undermines mitochondrial structure and function via modulation of mPTP opening and CL levels, and suggests that morphological analysis of isolated mitochondria by AFM is a useful approach for evaluating mitochondrial injury.

8 Article Age-dependent alpha-synuclein accumulation is correlated with elevation of mitochondrial TRPC3 in the brains of monkeys and mice. 2017

Chen, Min / Liu, Jia / Lu, Yongquan / Duan, Chunli / Lu, Lingling / Gao, Ge / Chan, Piu / Yu, Shun / Yang, Hui. ·Key Laboratory of Neural Regeneration and Repair, Department of Neurobiology, Capital Medical University, 10 Xi Tou Tiao, You Anmen, Beijing, 100069, China. · Center for Parkinson's Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China. · Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China. · Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing, China. yushun103@163.com. · Center for Parkinson's Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China. yushun103@163.com. · Key Laboratory of Neural Regeneration and Repair, Department of Neurobiology, Capital Medical University, 10 Xi Tou Tiao, You Anmen, Beijing, 100069, China. huiyang@ccmu.edu.cn. · Center for Parkinson's Disease Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China. huiyang@ccmu.edu.cn. ·J Neural Transm (Vienna) · Pubmed #27904950.

ABSTRACT: Aberrant α-synuclein (α-syn) accumulation has been shown to impair mitochondrial function by reducing mitochondrial membrane potential (MMP). However, the underlying mechanisms remain elusive. Transient receptor potential canonical (TRPC) channels are a diverse group of non-selective Ca

9 Article Piperine induces autophagy by enhancing protein phosphotase 2A activity in a rotenone-induced Parkinson's disease model. 2016

Liu, Jia / Chen, Min / Wang, Xue / Wang, Yi / Duan, Chunli / Gao, Ge / Lu, Lingling / Wu, Xia / Wang, Xiaomin / Yang, Hui. ·Department of Neurobiology, Capital Medical University, Center for Parkinson's Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, China. · Department of Clinical Laboratory, China Rehabilitation Research Center, School of Rehabilitation Medicine, Capital Medical University, Beijing, China. · School of Traditional Chinese Medicine, Capital Medical University, Beijing, China. ·Oncotarget · Pubmed #27572322.

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder, but there are few treatments currently available. The autophagy pathway plays an important role in the pathogenesis of PD; modulating this pathway is considered to be a promising treatment strategy. Piperine (PIP) is a Chinese medicine with anti-inflammatory and antioxidant effects. The present study investigated the neuroprotective effects of PIP on rotenone-induced neurotoxicity in SK-N-SH cells, primary rat cortical neurons, and in a mouse model. Mice were administered rotenone (10mg/kg) for 6 weeks; PIP (25mg/kg, 50mg/kg) was subsequently administered for 4 weeks. We found that PIP treatment attenuated rotenone-induced motor deficits, and rescued the loss of dopaminergic neurons in the substantia nigra. PIP increased cell viability and restored mitochondrial functioning in SK-N-SH cells and primary neurons. In addition, PIP induced autophagy by inhibiting mammalian target of rapamycin complex 1(mTORC1) via activation of protein phosphotase 2A (PP2A). However, inhibiting PP2A activity with okadaic acid reduced these protective effects, suggesting that PP2A is a target of PIP. These findings demonstrate that PIP exerts neuroprotective effects in PD models via induction of autophagy, and may be an effective agent for PD treatment.

10 Article DJ-1/PARK7, But Not Its L166P Mutant Linked to Autosomal Recessive Parkinsonism, Modulates the Transcriptional Activity of the Orphan Nuclear Receptor Nurr1 In Vitro and In Vivo. 2016

Lu, Lingling / Zhao, Shasha / Gao, Ge / Sun, Xiaohong / Zhao, Huanying / Yang, Hui. ·Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China. · Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China. huiyang@ccmu.edu.cn. · Center of Parkinson's Disease, Beijing Institute of Brain Disorders, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, 10 You an men Wai, Xitoutiao, Beijing, 100069, China. huiyang@ccmu.edu.cn. ·Mol Neurobiol · Pubmed #26873851.

ABSTRACT: Although mutations of DJ-1 have been linked to autosomal recessive Parkinsonism for years, its physiological function and the pathological mechanism of its mutants are not well understood. We report for the first time that exogenous application of DJ-1, but not its L166P mutant, enhances the nuclear translocation and the transcriptional activity of Nurr1, a transcription factor essential for dopaminergic neuron development and maturation, both in vitro and in vivo. Knockdown of DJ-1 attenuates Nurr1 activity. Further investigation showed that signaling of Raf/MEK/ERK MAPKs is involved in this regulatory process and that activation induced by exogenous DJ-1 is antagonized by U0126, an ERK pathway inhibitor, indicating that DJ-1 modulates Nurr1 activity via the Raf/MEK/ERK pathway. Our findings shed light on the novel function of DJ-1 to enhance Nurr1 activity and provide the first insight into the molecular mechanism by which DJ-1 enhances Nurr1 activity.

11 Article GBA deficiency promotes SNCA/α-synuclein accumulation through autophagic inhibition by inactivated PPP2A. 2015

Du, Ting-Ting / Wang, Le / Duan, Chun-Li / Lu, Ling-Ling / Zhang, Jian-Liang / Gao, Ge / Qiu, Xiao-Bo / Wang, Xiao-Min / Yang, Hui. ·a Center of Parkinson Disease Beijing Institute for Brain Disorders; Key Laboratory for Neurodegenerative Disease of the Ministry of Education; Department of Neurobiology Capital Medical University ; Beijing , China. · b Key Laboratory of Cell Proliferation and Regulation Biology; Ministry of Education; College of Life Sciences; Beijing Normal University ; Beijing , China. ·Autophagy · Pubmed #26378614.

ABSTRACT: Loss-of-function mutations in the gene encoding GBA (glucocerebrosidase, β, acid), the enzyme deficient in the lysosomal storage disorder Gaucher disease, elevate the risk of Parkinson disease (PD), which is characterized by the misprocessing of SNCA/α-synuclein. However, the mechanistic link between GBA deficiency and SNCA accumulation remains poorly understood. In this study, we found that loss of GBA function resulted in increased levels of SNCA via inhibition of the autophagic pathway in SK-N-SH neuroblastoma cells, primary rat cortical neurons, or the rat striatum. Furthermore, expression of the autophagy pathway component BECN1 was downregulated as a result of the GBA knockdown-induced decrease in glucocerebrosidase activity. Most importantly, inhibition of autophagy by loss of GBA function was associated with PPP2A (protein phosphatase 2A) inactivation via Tyr307 phosphorylation. C2-ceramide (C2), a PPP2A agonist, activated autophagy in GBA-silenced cells, while GBA knockdown-induced SNCA accumulation was reversed by C2 or rapamycin (an autophagy inducer), suggesting that PPP2A plays an important role in the GBA knockdown-mediated inhibition of autophagy. These findings demonstrate that loss of GBA function may contribute to SNCA accumulation through inhibition of autophagy via PPP2A inactivation, thereby providing a mechanistic basis for the increased PD risk associated with GBA deficiency.

12 Article α-Synuclein amino terminus regulates mitochondrial membrane permeability. 2014

Shen, Jiamei / Du, Tingting / Wang, Xue / Duan, Chunli / Gao, Ge / Zhang, Jianliang / Lu, Lingling / Yang, Hui. ·Center for Parkinson׳s Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China. · Center for Parkinson׳s Disease, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Department of Neurobiology Capital Medical University, Beijing 100069, China. Electronic address: huiyang@ccmu.edu.cn. ·Brain Res · Pubmed #25446002.

ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative movement disorder affecting an increasing number of elderly. Various studies have shown that mitochondrial dysfunction and abnormal protein aggregation are two major contributors to the progression of PD. The N terminus of α-synuclein (α-Syn/N), which adopts an α-helical conformation upon lipid binding, is essential for membrane interaction; yet its role in mitochondria remains poorly defined. A functional characterization of the α-Syn N-terminal domain and investigation of its effect on mitochondrial membrane permeability were undertaken in this study. α-Syn/N and α-Syn/delN (amino acids 1-65 and 61-140, respectively) constructs were overexpressed in dopaminergic MN9D cells and primary cortical neurons. A decrease in cell viability was observed in cells transfected with α-Syn/N but not α-Syn/delN. In addition, an α-Syn/N-induced increase in the level of intracellular reactive oxygen species, alteration in mitochondrial morphology, and decrease in mitochondrial membrane potential were accompanied by the activation of mitochondrial permeability transition pores (mPTP). These changes were also associated with a decline in mitochondrial cardiolipin content and interaction with the voltage-dependent anion channel and adenine nucleotide translocator in the mitochondrial membrane. The activation of mPTPs and reduction in cell viability were partially reversed by bongkrekic acid, an inhibitor of adenine nucleotide translocator (ANT), suggesting that the interaction between α-Syn and ANT promoted mPTP activation and was toxic to cells. BKA treatment reduced interaction of α-Syn/N with ANT and VDAC. These results suggest that the N terminus of α-Syn is essential for the regulation of mitochondrial membrane permeability and is a likely factor in the neurodegeneration associated with PD.

13 Article Protective effect of SIRT1 on toxicity of microglial-derived factors induced by LPS to PC12 cells via the p53-caspase-3-dependent apoptotic pathway. 2013

Ye, Jieming / Liu, Zhenhua / Wei, Jipeng / Lu, Lingli / Huang, Yanjun / Luo, Lili / Xie, Huifang. ·Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. ·Neurosci Lett · Pubmed #23973301.

ABSTRACT: Sirtuin1 (SIRT1) has protective effects in some neurodegenerative disease models, but it is not clear whether SIRT1 play the same role on inflammation-mediated Parkinson's disease (PD) models. In this study, we firstly established an inflammation environment by stimulating microglial BV-2 cells with the inflammatory agent lipopolysaccharides (LPS), which demonstrated by increasing of the levels of TNF-a, and IL-6 in cultured medium. Then we exposed PC12 cells (a model of catecholaminergic neuronal cells) with the supernant from LPS stimulated BV-2 cells (activated BV-2). PC12 cell apoptosis and SIRT1 involved protection were investigated. The results indicated that treatment with LPS caused significant decrease in SIRT1 expression in activated BV-2 cells, and increased the levels of TNF-a and IL-6, as measured by ELISA, whereas resveratrol (a known SIRT1 activator) suppressed this effect, which was conversely strengthened by sirtinol (a SIRT1 inhibitor), suggesting that SIRT1 may be involved in regulating proinflammatory cytokines from microglial activation. Further, we found that factors derived from activated microglia significantly decreased the level of deacetylation of p53 by reducing the expression of SIRT1, an effect that increased the apoptosis of PC12 and reduced cell viability. The addition of resveratrol could protect PC12 cells from inflammation-mediated damage above-mentioned, while nicotinamide (another SIRT1 inhibitor) treatment had the opposite effect of resveratrol. Together, these data suggests that: SIRT1 inhibits LPS-mediated proinflammatory cytokines release in microglia, and circumvents dopaminergic neurons injury induced by activated microglial-derived factors via p53-caspase-3-dependent mechanism of apoptosis. Thus, upregulation of SIRT1 provides a promising research field for therapeutic intervention in neuroinflammation diseases.