Monoamine oxidase-B (MAO-B) has been determined to be the enzyme responsible for the conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into its toxic metabolite 1-methyl-4-phenylpyridine ion (MPP+). Since this enzyme has been localized primarily in astrocytes and serotonergic neurons, it would appear that MPP+ is being produced outside the dopaminergic neurons. To investigate this possibility, the administration of MPTP was preceded by systemically administered fluoxetine. In keeping with its demonstrated ability to inhibit uptake into serotonergic neurons and serotonin uptake into astrocytes, fluoxetine pretreatment resulted in a significant attenuation of MPTP-induced depletions of striatal dopamine and serotonin concentration. These results support the extra-dopaminergic production of MPP+.
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http://dx.doi.org/10.1007/BF01245250 | DOI Listing |
Chin J Nat Med
January 2025
Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:
Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice.
View Article and Find Full Text PDFActa Neurobiol Exp (Wars)
January 2025
Ondokuz Mayıs University, School of Medicine, Department of Biochemistry, Samsun, Turkey.
Neuroinflammation and the immune response are recognized as significant mechanisms contributing to the progression and pathophysiology of Parkinson's disease (PD). Consequently, extensive research is being conducted on drugs targeting inflammation and immune response. Leflunomide, known for its anti‑inflammatory and immunomodulatory properties, is currently used as a disease‑modifying agent for the treatment of rheumatoid arthritis.
View Article and Find Full Text PDFParkinsons Dis
December 2024
School of Medicine, Henan University of Chinese Medicine, Zhengzhou, China.
Cinnamaldehyde (CA), the primary bioactive compound in cinnamon ( Presl, Lauraceae, ), holds potential therapeutic benefits for Parkinson's disease (PD). To scrutinize the impact and mechanisms of CA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD, male C57BL/6 mice were randomly allocated to CA (150, 300, and 600 mg/kg), model, Madopar, and control group ( = 12). The Open Field, Pole-jump, and Rotarod experiments assessed exercise capacity and anxiety levels.
View Article and Find Full Text PDFCell Death Discov
December 2024
Department of Histoembryology, School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong Province, China.
Neuroinflammation induced by activation of microglial is a vital contributor to progression of Parkinson's disease (PD), emerging evidences suggested that ferroptosis played a pivotal role in microglial activation and subsequent dopaminergic neuron loss. Nevertheless, the fundamental pathogenesis of that ferroptosis contributes to PD is not yet sufficiently understood. Based on GEO dataset, ferroptosis related genes were found to be enriched in PD patients and MPTP mouse model of PD, among them, ATF4 was found to be dramatically differentially expressed.
View Article and Find Full Text PDFMetab Brain Dis
December 2024
Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, 02447, Seoul, Republic of Korea.
Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons. In particular, neuroinflammation associated with phosphorylation of c-Jun N-terminal kinase (JNK) is likely to cause the death of dopaminergic neurons. Therefore, protecting dopaminergic neurons through anti-neuroinflammation is a promising therapeutic strategy for PD.
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