Evidence map›Paper›PMID 23438839›Full record

ReviewNature reviews. Endocrinology2013

Neurosteroids as regenerative agents in the brain: therapeutic implications.

Roberta D Brinton

Registry-linked trialOpen access · greenAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Nature reviews. Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04838301 (Safety and Efficacy of Allopregnanolone), which is not on this map. Cited by 88 papers.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed
10.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04838301 phase2active not recruitingnot on this mapstarted 2023, after this paper: background citation

Safety and Efficacy of Allopregnanolone (Allo) as a Regenerative Therapeutic for Alzheimer's Disease: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Clinical Trial

TypeinterventionalSponsorUniversity of ArizonaRan2023 to 2027Enrolled100ConditionsAlzheimer Dementia, Late Onset Alzheimer Disease, Neurodegenerative DiseasesArmsAllopregnanolone, Placebo
3 · Its place in the literature

Who cites it

88 citing papers in PubMed, 153 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Trial
  4. Trial
  5. Trial
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. The role of lipid metabolism in cognitive impairment.Arquivos de neuro-psiquiatria · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Review

28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

1 author at 1 institution in 1 country.

Roberta D BrintonDepartment of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA. rbrinton@usc.edu
University of Southern California · US

Funding

LOS ANGELES BASIN CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR031986 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BUCHANAN, THOMAS A · 2010 to 2011
$21.1M
Development of Allopregnanolone as a Neurogenic Regenerative TherapeuticU01AG031115 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI BRINTON, ROBERTA EILEEN · 2008 to 2012
$2.4M
NCRR NIH HHS UL1 RR031986NIA NIH HHS U01 AG031115
6 · The paper itself

Abstract

Regenerative therapeutics hold the promise of self-renewal and repair. Ageing and age-associated neurodegenerative diseases are marked by a decline in self-renewal and repair, but a capacity for regeneration is retained. The challenge faced by researchers developing molecular therapeutics to promote self-renewal in the nervous system is to activate regenerative and repair pathways often in the context of progressive degeneration. Neurosteroids regulate both regeneration and repair systems in the brain, and among this class of molecules, allopregnanolone has been broadly investigated for its role to promote regeneration in both the central and peripheral nervous systems. In the brain, allopregnanolone induced generation and survival of new neurons in the hippocampus of both aged mice and mice with Alzheimer disease, accompanied by restoration of associative learning and memory function. In the brain of mice with Alzheimer disease, allopregnanolone increased liver X receptor and pregnane X receptor expression, reduced amyloid-β and microglial activation, and increased markers of myelin and white matter generation. Therapeutic windows for efficacy of allopregnanolone were evident in the brains of mice with both normal ageing and Alzheimer disease. Allopregnanolone dose and a regenerative treatment regimen of intermittent allopregnanolone exposure were determining factors regulating therapeutic efficacy. Allopregnanolone serves as proof of concept for therapeutics that target endogenous regeneration, windows of therapeutic opportunity for regeneration, and critical system biology factors that will determine the efficacy of regeneration.

Indexed as

Alzheimer DiseaseAnimalsBrainHumansNeurotransmitter AgentsPregnanoloneNeurotransmitter AgentsPregnanolone

Identifiers

PMID23438839
PMCPMC9936614
OpenAlexW2101301851

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.