S‐adenosyl methionine improves motor co‐ordination with reduced oxidative stress, dopaminergic neuronal loss, and DNA methylation in the brain striatum of 6‐hydroxydopamine‐induced neurodegeneration in rats

Abstract

Purpose Parkinson's disease (PD) is the most common age‐related neurodegenerative disease worldwide. S‐adenosyl methionine (SAMe), a methyl donor that plays an important role in DNA methylation, could replenish the cellular antioxidant glutathione (GSH). Herein, we investigated the neuroprotective effects of SAMe in 6‐hydroxydopamine (6‐OHDA) rat models of PD and elucidated the underlying mechanism. Methods PD model rats were developed by injecting 6‐OHDA stereotaxically into the striatum. In Phase 1 of the study, we performed the neurobehavioral tests, GSH assay, and histopathology to evaluate the neuroprotective effects of SAMe. The animals were treated with SAMe (150 or 300 mg/kg body weight) orally for 28 days. The positive control group received selegiline (5 mg/kg), whereas the disease control group received normal saline. In Phase 2, we evaluated the striatal dopamine levels and performed DNA methylation assay to uncover the mechanism of action of SAMe. In this phase, a higher dose of SAMe (300 mg/kg) was used. Results SAMe (300 mg/kg) treatment for 4 weeks significantly attenuated the abnormal circling behavior in PD rats (p < 0.05). Moreover, SAMe at both doses (150 and 300 mg/kg) enhanced the performance of PD rats in the open field test and stepping test (p < 0.05). SAMe treatment significantly increased the GSH levels, and at high dose, SAMe restricted neuronal loss in the striatum of PD‐model rats (p < 0.05). Moreover, SAMe treatment led to a significant recovery in the dopamine levels and improved the DNA methylation status in the dopaminergic neurons (p < 0.05) of PD model rats. Conclusion SAMe exhibits antioxidant activity and DNA methylation modulating effects in 6‐OHDA model PD rats. Moreover, SAMe prevents neuronal loss in PD rats suggesting that SAMe has therapeutic potential in preventing PD development. The neuroprotective potential of SAMe is greater at high doses.

Targeted improvement of plant‐based protein: Genome‐wide association mapping of a lentil (Lens culinaris Medik.) diversity panel

“…The body can synthesize Cys from Met; consequently, they are combined for intake requirements. Cys is vital in protein folding because of its ability to form disulfide bonds; Met is significant for its role as the AA that begins translation as well for its derivatives, glutathione, and S‐adenosyl methionine (SAM), which are important in oxidative protection and DNA methylation, respectively, and have been examined in such diverse pathologies as obesity and Parkinson's disease (Barbosa et al, 2021; Jalgaonkar et al, 2022). In addition to AA composition, protein quality also depends on PDg, which determines how well the protein can be catabolized during digestion and utilized by the body.…”

Exploratory focused pharmacogenetic testing reveals novel markers associated with risperidone pharmacokinetics in Saudi children with autism

“…This reaction is part of the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds, such as neurotransmitters (dopamine and serotonin) ( Jalgaonkar et al, 2022 ; Majhi et al, 2023 ). Individuals homozygous for the SNP rs1801133 (MTHFR_c.665C>T(Ala222Val)) have lower MTHFR activity than CC or CT (heterozygous) individuals and therefore are predisposed to hyperhomocysteinemia associated with lower plasma folate levels ( Majhi et al, 2023 ).…”