Monoamine Oxidase B in Astrocytic GABA Synthesis: A Central Mechanism in Neurodegeneration and Neuroinflammation

Monoamine oxidase B (MAO-B) is a mitochondrial enzyme predominantly expressed in astrocytes, where it plays a crucial role in neurotransmitter metabolism, oxidative stress regulation, and neuroinflammation. In addition to its well-characterized function in the oxidative deamination of monoamines such as dopamine, noradrenaline, and serotonin, MAO-B is increasingly recognized for its involvement in astrocytic GABA synthesis. In reactive astrocytes, upregulated MAO-B activity enhances GABA production, leading to excessive tonic inhibition that disrupts neuronal excitability and synaptic function. Moreover, MAO-B-mediated metabolism generates reactive oxygen species (ROS), including hydrogen peroxide, further exacerbating oxidative stress and neuroinflammation. This article examines the critical role of MAO-B in neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke, emphasizing its contribution to impaired GABAergic signaling and neurodegeneration. Finally, it explores the potential of MAO-B inhibition as a targeted therapeutic approach to regulate astrocytic GABA synthesis, mitigate aberrant inhibitory signaling, and restore neural circuit homeostasis in neurodegenerative and metabolic disorders.