当前位置： SCI文献检索 > JOURNAL OF BIOMEDICAL SCIENCE期刊下所有文献 > Lithospermic acid attenuates 1-methyl-4-phenylpyridine-induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways.

Lithospermic acid attenuates 1-methyl-4-phenylpyridine-induced neurotoxicity by blocking neuronal apoptotic and neuroinflammatory pathways.

Abstract：

BACKGROUND:Parkinson's disease is the second most common neurodegenerative disorders after Alzheimer's disease. The main cause of the disease is the massive degeneration of dopaminergic neurons in the substantia nigra. Neuronal apoptosis and neuroinflammation are thought to be the key contributors to the neuronal degeneration. RESULTS:Both CATH.a cells and ICR mice were treated with 1-methyl-4-phenylpyridin (MPP(+)) to induce neurotoxicity in vitro and in vivo. Western blotting and immunohistochemistry were also used to analyse neurotoxicity, neuroinflammation and aberrant neurogenesis in vivo. The experiment in CATH.a cells showed that the treatment of MPP(+) impaired intake of cell membrane and activated caspase system, suggesting that the neurotoxic mechanisms of MPP(+) might include both necrosis and apoptosis. Pretreatment of lithospermic acid might prevent these toxicities. Lithospermic acid possesses specific inhibitory effect on caspase 3. In mitochondria, MPP(+) caused mitochondrial depolarization and induced endoplasmic reticulum stress via increasing expression of chaperone protein, GRP-78. All the effects mentioned above were reduced by lithospermic acid. In animal model, the immunohistochemistry of mice brain sections revealed that MPP(+) decreased the amount of dopaminergic neurons, enhanced microglia activation, promoted astrogliosis in both substantia nigra and hippocampus, and MPP(+) provoked the aberrant neurogenesis in hippocampus. Lithospermic acid significantly attenuates all of these effects induced by MPP(+). CONCLUSIONS:Lithospermic acid is a potential candidate drug for the novel therapeutic intervention on Parkinson's disease.

journal_name

J Biomed Sci

journal_title

Journal of biomedical science

authors

Lin YL,Tsay HJ,Lai TH,Tzeng TT,Shiao YJ

doi

10.1186/s12929-015-0146-y

subject

Has Abstract

pub_date

2015-05-28 00:00:00

pages

37

eissn

1021-7770

issn

1423-0127

pii

10.1186/s12929-015-0146-y

journal_volume

22

pub_type

杂志文章

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