Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of the dopaminergic neurons in substantia nigra, presumably due to increased apoptosis and oxidative stress. To investigate whether PD-induced survival/apoptosis gene expression changes can serve as prognostic biomarkers of PD, we measured expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt pathway factors and additional apoptotic and anti-apoptotic factors in peripheral blood mononuclear cells (PBMC) of PD patients (n=50) and healthy controls (n=50) by real time PCR. Expression levels of apoptotic factors phosphatase and tensin homolog (PTEN) and mitochondrial apoptosis-inducing factor 1 (AIFM1) were significantly decreased, anti-apoptotic factors DJ-1 and Akt-1 were significantly increased and anti-apoptotic Bcl-2 was significantly decreased in PD patients. Expression levels of AIFM1 were significantly correlated with Hoehn-Yahr scores. Moreover, PD patients with postural instability showed significantly reduced expression levels of anti-apoptotic DJ-1, Akt-1 and mTOR than PD patients without postural instability. Expression profiles of brain samples of mice with rotenone-induced PD model and PBMC samples of PD patients showed remarkable resemblance. Our results indicate that the anti-apoptotic PI3K/Akt pathway is over activated in PD, presumably as an effort to compensate for increased neuronal apoptosis and oxidative stress. By contrast, patients with postural instability show reduced anti-apoptotic factor expression suggesting that this compensating mechanism fails in patients with this particular motor symptom. PBMC expression levels of AIFM1 might serve as a biomarker of disability and disease progression in PD.
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PMID:Expression changes of genes associated with apoptosis and survival processes in Parkinson's disease. 2680 67

Depression is a common non-motor symptom in patients with Parkinson's disease (PD) and difficult to treat. Crocin is a natural multipotential neuroprotective compound that has been shown to elicit antidepressant activity and is promising for the therapy of neuropsychological diseases. Here, we investigated the therapeutic effect of crocin in a mouse model of Parkinson's disease depression (PDD) and clarified the underlying mechanism. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute mouse model of PD, and found that around 60% of the model mice showed depression-like behavior, using the forced swimming test (FST). A regime of 10-day treatment of crocin alleviated the PDD symptoms. The crocin reduced the structural damage in soma volume and axon length of neurons and inhibited their spontaneous discharge in dopaminergic (DA) neurons in the ventral tegmental area (VTA). Notably, the MPTP-treated mice showed the decrease in the critical signaling for synaptic plasticity, including the proteins of PSD-95, synapsin-1, and GluR-1, in the medial prefrontal cortex (mPFC) where it receives efferent from VTA and regulates depression-like behavior. However, crocin treatment rescued the defect of the mammalian target of rapamycin (mTOR) signaling in PDD mice. Furthermore, the antidepressant action of crocin was blunted after blockade of mTOR signaling with the antagonist rapamycin. In conclusion, our study demonstrated that crocin protected the DA projection neurons in the VTA through activating mTOR, which subsequently improved the neural synaptic plasticity of mPFC, and ameliorated depression-like behavior in PD mice.
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PMID:Crocin Reverses Depression-Like Behavior in Parkinson Disease Mice via VTA-mPFC Pathway. 3249 80