https://transhumanist.ru/index.php?action=history&feed=atom&title=MAOB 2026-04-09T07:08:27Z История изменений этой страницы в вики MediaWiki 1.43.6 https://transhumanist.ru/index.php?title=MAOB&diff=4640&oldid=prev 2021-04-29T19:27:42Z

<p>Новая страница: «Amine oxidase [flavin-containing] B (EC 1.4.3.4) (Monoamine oxidase type B) (MAO-B) ==Publications== {{medline-entry |title=Modulation of <a href="/index.php?title=KDM1A&amp;action=edit&amp;redlink=1" class="new" title="KDM1A (страница не существует)">KDM1A</a> with vafidem...»</p> <p><b>Новая страница</b></p><div>Amine oxidase [flavin-containing] B (EC 1.4.3.4) (Monoamine oxidase type B) (MAO-B)<br /> <br /> ==Publications==<br /> <br /> {{medline-entry<br /> |title=Modulation of [[KDM1A]] with vafidemstat rescues memory deficit and behavioral alterations.<br /> |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32469975<br /> |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&#039;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&#039;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.<br /> |mesh-terms=* Aging<br /> * Alzheimer Disease<br /> * Animals<br /> * Behavior, Animal<br /> * Brain<br /> * Disease Models, Animal<br /> * Enzyme Inhibitors<br /> * Epigenesis, Genetic<br /> * Female<br /> * Gene Expression<br /> * Hippocampus<br /> * Histone Demethylases<br /> * Humans<br /> * Male<br /> * Memory Disorders<br /> * Mice<br /> * Mice, Inbred C57BL<br /> * Mice, Mutant Strains<br /> * Monoamine Oxidase Inhibitors<br /> * Oxadiazoles<br /> * Rats<br /> * Rats, Sprague-Dawley<br /> <br /> |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259601<br /> }}</div>

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