Monoamine oxidase-B (MAOB) has been believed to mediate the degradation of monoamine neurotransmitters such as dopamine. However, this traditional belief has been challenged by demonstrating that it is not MAOB but MAOA which mediates dopamine degradation. Instead, MAOB mediates the aberrant synthesis of GABA and hydrogen peroxide (HO) in reactive astrocytes of Parkinson's disease (PD). Astrocytic GABA tonically suppresses the dopaminergic neuronal activity, whereas HO aggravates astrocytic reactivity and dopaminergic neuronal death. Recently discovered reversible MAOB inhibitors reduce reactive astrogliosis and restore dopaminergic neuronal activity to alleviate PD symptoms in rodents. In this perspective, we redefine the role of MAOB for the aberrant suppression and deterioration of dopaminergic neurons through excessive GABA and HO synthesis of reactive astrocytes in PD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028367 | PMC |
| http://dx.doi.org/10.3390/ijms23084453 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Examining structure-activity relationships of ManNAc analogs used in the metabolic glycoengineering of human neural stem cells.
Biomater Adv
December 2024
Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Whiting School of Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:
This study defines biochemical mechanisms that contribute to novel neural-regenerative activities we recently demonstrated for thiol-modified ManNAc analogs in human neural stem cells (hNSCs) by comparing our lead drug candidate for brain repair, "TProp," to a "size-matched" N-alkyl control analog, "But." These analogs biosynthetically install non-natural sialic acids into cell surface glycans, altering cell surface receptor activity and adhesive properties of cells. In this study, TProp modulated sialic acid-related biology in hNSCs to promote neuronal differentiation through modulation of cell adhesion molecules (integrins α6, β1, E-cadherin, and PSGL-1) and stem cell markers.
View Article and Find Full Text PDFTreadmill intervention attenuates motor deficit with 6-OHDA-induced Parkinson's disease rat via changes in lipid profiles in brain and muscle.
Aging (Albany NY)
January 2025
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
One of the key hallmarks of Parkinson's disease is the disruption of lipid homeostasis in the brain, which plays a critical role in neuronal membrane integrity and function. Understanding how treadmill training impacts lipid restructuring and its subsequent influence on motor function could provide a basis for developing targeted non-pharmacological interventions for individuals living with early stage of PD. This study aims to investigate the effects of a treadmill training intervention on motor deficits induced by 6-OHDA in rats model of PD.
View Article and Find Full Text PDFType 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors.
Neurosci Bull
January 2025
Center for Translational Neuromedicine and Neurology, School of Life Sciences, Institute for Brain Sciences Research, Henan University, Huaihe Hospital of Henan University, Kaifeng, 475004, China.
Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism.
View Article and Find Full Text PDFThe Intricate Interplay: Microbial Metabolites and the Gut-Liver-Brain Axis in Parkinson's Disease.
J Neurosci Res
January 2025
Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Kochi, Kerala, India.
Parkinson's Disease (PD) is a neurodegenerative disorder marked by the depletion of dopaminergic neurons. Recent studies highlight the gut-liver-brain (GLB) axis and its role in PD pathogenesis. The GLB axis forms a dynamic network facilitating bidirectional communication between the gastrointestinal tract, liver, and central nervous system.
View Article and Find Full Text PDFSystemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice.
NPJ Parkinsons Dis
January 2025
Department of Neuroscience & Experimental Therapeutics, Texas A&M University College of Medicine, 8447 John Sharp Pkwy, Bryan, TX, 77807-3260, USA.
The smoking cessation drug cytisine exerts neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of female but not male 6-hydroxydopamine (6-OHDA) lesioned parkinsonian mice. To address the important question of whether circulating 17β-estradiol mediates this effect, we employ two mouse models aimed at depleting systemically circulating 17β-estradiol: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating 17β-estradiol in female 6-OHDA lesioned parkinsonian mice results in the loss of cytisine-mediated neuroprotection as measured using apomorphine-induced contralateral rotations and SNc DA neurodegeneration.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!