Background and purpose: Parkinson's disease (PD), a common neurodegenerative disorder with motor and nonmotor symptoms, does not have effective treatments.Dietary tryptophan (Trp) supplementation has potential benefits for the treatment of multiple disorders. However, whether additional Trp in the diet could be beneficial for PD remains to beinvestigated. In the present study, the neuroprotective role of dietary Trp on a rotenone-induced rat model of PD was determined. Methods:The rotenone was injected to build the PD model, and then the rats were treated with Trp in the diet. And then, an open field test, western blot analysis, and enzyme linked immunosorbent assay (ELISA) were performed. Results:We observed that dietary Trp significantly ameliorated impaired motor function, upregulated tyrosine hydroxylase expression, inhibited the nuclear transport of Nuclear factor-kappa B (NF-κB) in substantia nigra (SN), and downregulated the protein levels of IL-1β, IL-6, and TNF-α in serum in rotenone-treated rats. However, these patterns were reversed in response to treatment with ampicillin, an agent that can clean intestinal Trp metabolism flora. Moreover, after using CH223191, an inhibitor of the aromatic hydrocarbon receptor (AhR) pathway, dietary Trp could not exert neuroprotective roles in the rotenone-induced rat model of PD. Conclusion:These results suggest that Trp in the diet can protect against rotenoneinduced neurotoxicity to ameliorate motor deficits, which may be mediated through activating AhR pathway. K E Y W O R D Saromatic hydrocarbon receptor pathway, dietary tryptophan, Parkinson's disease INTRODUCTIONParkinson's disease (PD) is the second most common neurodegenerative disease, and is increasingly receiving attention from multipleThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Parkinson's disease (PD) is a well-known neurodegenerative disorder characterized by the degeneration of dopaminergic neurons, and oxidative stress and neuroinflammation are also associated with the pathogenesis of PD. Mitochonic acid 5 , an analogue of indole-3-acetic acid, exerts key protective roles in inhibiting apoptosis, oxidative stress and neuroinflammation in multiple diseases. However, whether MA-5 can be beneficial for PD remains unclear. Hence, the aim of this study was to investigate the neuroprotective role of MA-5 in PD. In the current study, MPTP-challenged mice were treated as the in vivo model, and the effect of MA-5 on the motor function, neuronal survival, oxidative stress, neuroinflammation and the underlying mechanisms involved with AMPK and autophagy were determined. We revealed that MA-5 obviously up-regulated the phosphorylation of AMPK and promoted the autophagy (indicated by the increased LC3II/LC3I, parkin, pink and decreased p62) in substantia nigra (SN), ameliorated the motor deficits, up-regulated the expression of TH, suppressed the inflammation (indicated by the decreased protein levels of interleukin (IL)-1β, IL-6, tumour necrosis factor α) in SN in MPTP-induced mice. However, these patterns were reversed after the treatment of Compound C, an inhibitor of AMPK; also, after the application of CSA, an inhibitor of autophagy, MA-5 cannot play against the neurotoxicity of MPTP in mice. These combined results suggest that MA-5 can protect against MPTP-induced neurotoxicity to ameliorate the impaired motor function, which may be modulated via activation of AMPK-induced autophagy.

Effective strategies are needed to prevent the development of neuroinflammation, which is associated with nervous system disease, in patients. A previous study indicated that mitochonic acid 5 (MA‑5) may promote the survival of microglial cells via mitofusin 2 (Mfn2)‑associated mitophagy in response to lipopolysaccharide (LPS)‑induced inflammation. The current study investigated the role and underlying mechanisms of MA‑5 in the migration of BV‑2 cells following LPS‑mediated inflammation. The results of the present study revealed that MA‑5 promoted migration and upregulated the expression of F‑actin, C‑X‑C motif chemokine receptor (CXCR) 4 and CXCR7 in BV‑2 cells in response to LPS‑induced inflammation. The results also indicate that MA‑5 did not promote migration or upregulate the expression of F‑actin, CXCR4 or CXCR7 following the inhibition of Mfn2. Overall, the results of the present study suggest that MA‑5 may promote the migration of microglial cells via Mfn2‑associated mitophagy following LPS‑induced inflammation.

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