Редактирование: MAOB

Amine oxidase [flavin-containing] B (EC 1.4.3.4) (Monoamine oxidase type B) (MAO-B)

==Publications==

{{medline-entry
|title=Modulation of [[KDM1A]] with vafidemstat rescues memory deficit and behavioral alterations.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32469975
|abstract=Transcription disequilibria are characteristic of many neurodegenerative diseases. The activity-evoked transcription of immediate early genes (IEGs), important for neuronal plasticity, memory and behavior, is altered in CNS diseases and governed by epigenetic modulation. [[KDM1A]], a histone 3 lysine 4 demethylase that forms part of transcription regulation complexes, has been implicated in the control of IEG transcription. Here we report the development of vafidemstat (ORY-2001), a brain penetrant inhibitor of [[KDM1A]] and [[MAOB]]. ORY-2001 efficiently inhibits brain [[KDM1A]] at doses suitable for long term treatment, and corrects memory deficit as assessed in the novel object recognition testing in the Senescence Accelerated Mouse Prone 8 (SAMP8) model for accelerated aging and Alzheimer's disease. Comparison with a selective [[KDM1A]] or [[MAOB]] inhibitor reveals that [[KDM1A]] inhibition is key for efficacy. ORY-2001 further corrects behavior alterations including aggression and social interaction deficits in SAMP8 mice and social avoidance in the rat rearing isolation model. ORY-2001 increases the responsiveness of IEGs, induces genes required for cognitive function and reduces a neuroinflammatory signature in SAMP8 mice. Multiple genes modulated by ORY-2001 are differentially expressed in Late Onset Alzheimer's Disease. Most strikingly, the amplifier of inflammation [[S100A9]] is highly expressed in LOAD and in the hippocampus of SAMP8 mice, and down-regulated by ORY-2001. ORY-2001 is currently in multiple Phase IIa studies.
|mesh-terms=* Aging
* Alzheimer Disease
* Animals
* Behavior, Animal
* Brain
* Disease Models, Animal
* Enzyme Inhibitors
* Epigenesis, Genetic
* Female
* Gene Expression
* Hippocampus
* Histone Demethylases
* Humans
* Male
* Memory Disorders
* Mice
* Mice, Inbred C57BL
* Mice, Mutant Strains
* Monoamine Oxidase Inhibitors
* Oxadiazoles
* Rats
* Rats, Sprague-Dawley

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259601
}}