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)

Depression, a major cause of disability worldwide, is characterized by a complex and heterogeneous symptomatology. With this respect, cognitive deterioration represents a major problem that has a strong impact on a patient's function. Thus, within the context of a depressive phenotype, it is important to characterize the mechanisms that sustain cognitive dysfunctions and may represent an important target for pharmacological intervention. Here, using the chronic mild stress (CMS) paradigm of depression, we found that, independently from the anhedonic phenotype, CMS rats showed a deficit in the novel object recognition (NOR) test, which is associated with an inability to phosphorylate GluN2B subunit on Ser1303 and to activate the mTOR pathway. In agreement with the role of these systems in the control of local protein synthesis, we observed an increase phosphorylated eukaryotic elongation factor 2 (eEF2) in the crude synaptosomal fraction after the NOR test specifically in control animals. Since it has been demonstrated that peEF2 leads to the translation of specific mRNAs, we investigated if the gene-specific translational control depends on the presence of upstream open reading frame (uORF). Interestingly, we found a significant increase of oligophrenin-1 (2 uORFs) and of Bmal1 (7 uORFs) protein levels specifically in the control animals exposed to the NOR test. Our results demonstrated that the cognitive decline associated with stress exposure might be due to alterations in local protein translation of specific mRNAs, suggesting that a pharmacological intervention able to correct these defects might be useful in the improvement of deteriorated functions in patients with major depression and stress-related disorders.
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PMID:Chronic Mild Stress-Induced Alterations of Local Protein Synthesis: A Role for Cognitive Impairment. 2809

Brain derived neurotrophic factor (Bdnf) is the most diffuse neurotrophin in the central nervous system and it is crucial for the proper brain development and maintenance. Indeed, through the binding to its high affinity receptor TRKB and the activation of different intracellular cascades, it boosts cell survival, neurite growth and spine maturations mechanisms. Here, we evaluated if the chronic oral treatment for 10 days with a phytosomal preparation containing Centella asiatica L. and Curcuma longa L. could improve Bdnf levels in the prefrontal cortex of adult rats. Interestingly we found an increased expression of Bdnf with main effect of the treatment on the mTOR-S6 downstream signaling pathway. Accordingly, we found an increase in the expression of eukaryotic elongation factor (eEF2) with a shift towards the phosphorylated form thus increasing the transcription of Oligophrenin-1, a protein carrying the upstream Open Reading Frame (uORF) which reduction is paralleled by memory dysfunctions. These results show the ability of the phytosome to enhance mTOR-S6 regulated transcription and suggest the possibility to use this preparation in subjects with impairments in neuroplastic mechanisms, memory and cognitive abilities.
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PMID:Chronic Treatment with a Phytosomal Preparation Containing Centella asiatica L. and Curcuma longa L. Affects Local Protein Synthesis by Modulating the BDNF-mTOR-S6 Pathway. 3325 14