Allopregnanolone as a Therapeutic to Regenerate the Degenerated Brain

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

Neurosteroids regulate both regeneration and repair systems in the brain. Among this class of molecules, allopregnanolone (Allo) is the first regenerative therapeutic that has been extensively investigated in animal models and more recently in humans for its capacity to promote regeneration in the central and peripheral nervous system. In preclinical analyses, Allo induced generation and survival of new neurons in the hippocampus of aged mice and in transgenic mouse models of Alzheimer’s disease (AD), which was associated with restoration of learning and memory function. Allo is a proliferative factor for both neural stem cells and pre-progenitor oligodendrocytes, increasing both the number of newly generated cells and their survival. Safety characteristics of Allo regulation of neurogenesis indicate that the regenerative system it affects is tightly regulated with closely guarded thresholds for both activation and magnitude of proliferation. In the brain of mice with AD, Allo increased liver X receptor and pregnane X receptor expression, reduced ß-amyloid and microglial activation, and increased markers of white matter generation. Results of preclinical studies indicate that an optimal treatment regimen of Allo to promote endogenous regeneration is one that is administered once per week over the course of several months. Allo dose and frequency of exposure are determining factors regulating its therapeutic efficacy. Previous and current human safety exposure data supported by extensive preclinical efficacy data are strong foundations for the clinical development of Allo as a therapeutic to regenerate the degenerated brain.

Original languageEnglish (US)
Title of host publicationInternational Society of Gynecological Endocrinology Series
PublisherSpringer Nature
Pages111-123
Number of pages13
DOIs
StatePublished - 2019

Publication series

NameInternational Society of Gynecological Endocrinology Series
ISSN (Print)2197-8735
ISSN (Electronic)2197-8743

Keywords

  • Aging brain
  • Allopregnanolone
  • Neurodegeneration
  • Neurosteroid
  • Regeneration

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Obstetrics and Gynecology
  • Reproductive Medicine

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