This drove our attention to unravel the possible involvement of PI3k/Akt/mTOR pathway in the neuroprotective effect of crocin against rotenone (ROT)-induced PD in rats.
Our findings indicate that mTOR pathway is a useful target to promote recovery and that mGluR5 allosteric regulators may potentially be repurposed to selectively target this pathway to enhance neuroplasticity in patients with Parkinson's disease.
Further characterizing the dysregulation of mTOR pathway and the clinical translation of mTOR modulators in PD may offer exciting new avenues for future drug development.
Additionally, phosphatidylinositol-3-kinase (<i>PI3K</i>)/mammalian target of rapamycin (<i>mTOR</i>) expression were activated, and ubiquitin carboxy-terminal hydrolase L1 (<i>UCH-L1</i>) expression was upregulated in the EX-PD group.
These findings indicate that genetic variability in the mTOR pathway contributes to SNCA effects in a nonlinear epistatic manner to modulate differential AAO in PD, unraveling the contribution of this cascade in the pathogenesis of the disease.
Our results demonstrated that Apelin-36 protects against MPP<sup>+</sup>-induced cytotoxicity through PI3K/Akt/mTOR autophagy pathway in PD model in vitro, which provides a new theoretical basis for the treatment of PD.
In conclusion, these results demonstrated that downregulation of SNHG1 attenuated MPP<sup>+</sup>-induced decreases in LC3-II (an autophagic marker) levels and cytotoxicity through the miR-221/222/p27/mTOR pathway, suggesting that SNHG1 may be a therapeutic target for neuroprotection and disease treatment in PD.
We aim to investigate the effect of miR-181b on autophagy, particularly the involvement of miR-181b in the regulation of the phosphatase and tensin homolog (PTEN)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway and neuronal autophagy in a 1-methyl-4- phenylpyridinium iodide(MPP<sup>+</sup>)-induced cellular model of Parkinson's disease.
The pathways of mTOR and SIRT1 are closely integrated. mTOR forms the complexes mTOR Complex 1 and mTOR Complex 2 and can impact multiple neurodegenerative disorders that include Alzheimer's disease, Huntington's disease, and Parkinson's disease.
Here, we used a 6-hydroxydopamine (6-OHDA) mouse model of PD to examine the effects exerted on non-motor symptoms by inhibition of the mammalian target of rapamycin complex 1 (mTORC1), which is involved in the control of protein synthesis, cell growth, and metabolism.
Compared with the Parkinson's disease group, the moxibustion group showed significantly greater tyrosine hydroxylase immunoreactivity and expression of light chain 3-II protein in the substantia nigra, and their behavioral score, α-synuclein immunoreactivity, the expression of phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase (p-p70S6K) in the substantia nigra were significantly lower.
Here, we review recent progress in characterizing the association of mTOR signaling with PD risk factors and further discuss the potential roles of mTOR in PD.
The cause of DA neuronal loss in PD is still unclear; however, accumulating evidence suggests that treatment with certain flavonoids can induce neuroprotective properties, such as activation of mammalian target of rapamycin complex 1 (mTORC1) and anti-inflammatory activities in animal models of PD.
At the molecular level, nucleolar disruption results in increased p53 levels and downregulation of mammalian target of rapamycin (mTOR) activity, leading to mitochondrial dysfunction and increased oxidative stress, similar to PD.
The capacity of rapamycin to provide neuroprotection in PD models appears to arise from its selective suppression of some but not all actions of mTOR, as indicated by the contrasting finding that Torin1, a full catalytic mTOR inhibitor, is not protective and induces Akt dephosphorylation and neuron death.
We further showed that RTP801 and PD mimetics such as 6-OHDA trigger neuron death by suppressing activation of the key kinase mammalian target of rapamycin (mTOR).