Astrocytes and Therapeutics for Parkinson's Disease

Rappold, Phillip M.; Tieu, Kim

doi:10.1016/j.nurt.2010.07.001

Cited by 188 publications

(143 citation statements)

References 122 publications

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“…The mechanism of MPTP toxicity has been extensively studied and characterized (Dauer and Przedborski 2003;Rappold and Tieu 2010). Because MPTP is lipophilic, it can rapidly cross the blood -brain barrier.…”

Section: K Tieumentioning

confidence: 99%

“…1). MPP þ is released from the nigral and striatal astrocytes through the organic cation transporter 3 into the extracellular space (Cui et al 2009;Rappold and Tieu 2010) where it is taken up by the neighboring dopaminergic neurons and terminals through the dopamine transporter. Once accumulated in dopaminergic neurons, MPP þ induces neurotoxicity primarily by inhibiting complex I of the mitochondrial electron transport chain, resulting in ATP depletion and increased oxidative stress Mizuno et al 1987).…”

Section: K Tieumentioning

confidence: 99%

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A Guide to Neurotoxic Animal Models of Parkinson's Disease

Tieu¹

2011

Cold Spring Harbor Perspectives in Medicine

410

299

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Parkinson's disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway.

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Section: K Tieumentioning

confidence: 99%

Section: K Tieumentioning

confidence: 99%

A Guide to Neurotoxic Animal Models of Parkinson's Disease

Tieu¹

2011

Cold Spring Harbor Perspectives in Medicine

410

299

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“…Previously, studies of connexin phosphorylation have suggested that one or a small number of sites of modification strictly correspond to one molecular function; however, connexins undergoing multiple levels of multi-site phosphorylation are critical to improving the functions of connexin (30). The present study on rotenone-treated rats demonstrated the induction of phosphorylated Cx43 in astrocytes, which may be important since astrocytes exhibit direct, active and critical roles in mediating neuronal survival and function in various neurodegenerative disorders, including PD (17). The post-translational modification was inhibited by gastrodin via the suppression of Cx43 expression.…”

Section: Discussionmentioning

confidence: 50%

“…This PD model is superior for use in the present study on the effects of gastrodin on PD. Accumulating data have indicated the importance of astrocytes in Parkinsonism (15)(16)(17). It has also been demonstrated that several connexins are expressed in neurons and astrocytes, and these may be involved in the release of ATP and glutamate (18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Gastrodin ameliorates Parkinson’s disease by downregulating connexin 43

Wang

Liu

et al. 2013

Molecular Medicine Reports

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Abstract. Gastrodin, the predominant constituent of a Chinese herbal medicine, has been utilized in the prevention of Parkinson's disease (PD); however, its mechanism of action remains unknown. Astrocytes are involved in PD and are proposed to be coupled with gap junction connexin 43 (Cx43). To evaluate the effects of gastrodin on PD, the effect of gastrodin on Cx43 in astrocytes and in a PD model were observed. Different doses of gastrodin were added to the astrocyte culture medium or injected into the rotenone model of PD. The relative expression of Cx43 was determined by qPCR and western blot analysis, while gap junctional intercellular communication (GJIC) was quantified using fluorescence recovery after photobleaching (FRAP). The phosphorylated Cx43 was significantly inhibited by gastrodin and the quantity of GJIC was significantly downregulated compared with that of the control cells (P<0.05). In addition, in the rat model of PD induced by rotenone, phosphorylated Cx43 was selectively enhanced in the striatal and hippocampal regions. The enhanced activity was inhibited significantly by gastrodin treatment (P<0.01). Gastrodin results in the prevention of PD by reducing the expression of Cx43 and inhibiting the phosphorylation of Cx43; therefore, it may offer a potential therapeutic alternative for patients with PD.

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“…In recent years, much research on PD has focused on the astrocytic-neuronal crosstalk, suggesting that this interaction is important for future therapies against neurodegenerative processes. During brain damage events, astrocytes become transiently or permanently impaired, and the subsequent impact on neuronal cells may lead to pathological conditions such as PD [5][6][7].…”

Section: Introductionmentioning

confidence: 99%