1 min read

ID: 1118742

Short Link: https://gregory-ms.com/articles/1118742/

Discovery Date: 01 December 2022, 21:47:44 UTC

Published Date: 2022-12-01 00:00:00

Source: BioMedCentral

Link: https://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-022-00923-2

Manual Selection: true

Machine Learning Gaussian Naive Bayes Model: false

Abstract

jats:titleAbstract</jats:title>jats:sec jats:titleBackground</jats:title> jats:pPregnenolone (P5) is a neurosteroid that promotes microtubule polymerization. It also reduces stress and negative symptoms of schizophrenia, promotes memory, as well as recovery from spinal cord injury. P5 is the first substance in the steroid-synthetic pathway; it can be further metabolized into other steroids. Therefore, it is difficult to differentiate the roles of P5 versus its metabolites in the brain. To alleviate this problem, we synthesized and screened a series of non-metabolizable P5 derivatives for their ability to polymerize microtubules similar to P5.</jats:p> </jats:sec>jats:sec jats:titleResults</jats:title> jats:pWe identified compound #43 (3-beta-pregnenolone acetate), which increased microtubule polymerization. We showed that compound #43 modified microtubule dynamics in live cells, increased neurite outgrowth and changed growth cone morphology in mouse cerebellar granule neuronal culture. Furthermore, compound #43 promoted the formation of stable microtubule tracks in zebrafish developing cerebellar axons.</jats:p> </jats:sec>jats:sec jats:titleConclusions</jats:title> jats:pWe have developed compound #43, a nonmetabolized P5 analog, that recapitulates P5 functions in vivo and can be a new therapeutic candidate for the treatment of neurodevelopmental diseases.</jats:p> </jats:sec>

Noun Phrases in Title

  • A synthetic pregnenolone analog
  • microtubule dynamics
  • neural development
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