Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms23084453
Keywords
astrocyte; Parkinson's disease; MAOB; GABA; H2O2; dopamine
Funding
- Institute for Basic Science (IBS), Center for Cognition and Sociality [IBS-R001-D2]
- Ministry of Science and ICT [2018M3C7A1056897, 2022R1C1C1006167]
- Brain Research Program through the National Research Foundation of Korea (NRF)
- National Research Foundation of Korea [2022R1C1C1006167, 2018M3C7A1056897] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This study shows that in Parkinson's disease, MAOB is involved in the aberrant synthesis of GABA and H2O2 in reactive astrocytes, leading to gradual damage and death of dopaminergic neurons.
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 (H2O2) in reactive astrocytes of Parkinson's disease (PD). Astrocytic GABA tonically suppresses the dopaminergic neuronal activity, whereas H2O2 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 H2O2 synthesis of reactive astrocytes in PD.
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