β-Methylphenylalanine exerts neuroprotective effects in a Parkinson's disease model by protecting against tyrosine hydroxylase depletion.

We evaluated the neuroprotective effects of β-methylphenylalanine in an experimental model of rotenone-induced Parkinson's disease (PD) in SH-SY5Y cells and rats. Cells were pre-treated with rotenone (2.5 µg/mL) for 24 hours followed by β-methylphenylalanine (1, 10 and 100 mg/L) for 72 hours. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), mitochondrial fragmentation, apoptosis, and mRNA and protein levels of tyrosine hydroxylase were determined. In a rat model of PD, dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels, bradykinesia and tyrosine hydroxylase expression were determined. In rotenone-pre-treated cells, β-methylphenylalanine significantly increased cell viability and MMP, whereas ROS levels, apoptosis and fragmented mitochondria were reduced. β-Methylphenylalanine significantly increased the mRNA and protein levels of tyrosine hydroxylase in SH-SY5Y cells. In the rotenone-induced rat model of PD, oral administration of β-methylphenylalanine recovered DA and DOPAC levels and bradykinesia. β-Methylphenylalanine significantly increased the protein expression of tyrosine hydroxylase in the striatum and substantia nigra of rats. In addition, in silico molecular docking confirmed binding between tyrosine hydroxylase and β-methylphenylalanine. Our experimental results show neuroprotective effects of β-methylphenylalanine via the recovery of mitochondrial damage and protection against the depletion of tyrosine hydroxylase. We propose that β-methylphenylalanine may be useful in the treatment of PD.