Evidence map›Paper›PMID 23883342›Full record

ReviewExpert opinion on therapeutic targets2013

PDE4 as a target for cognition enhancement.

Wito Richter, Frank S Menniti, Han-Ting Zhang, Marco Conti

Open access · greenAbstract readReview
In one paragraph

Review in Expert opinion on therapeutic targets, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 2 pooled it
4.8field-weighted citation impact, top 4% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 143 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Single-cell analysis reveals neuroprotective histone deacetylase inhibitor pathways.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  15. PET imaging in rat brain shows opposite effects of acute and chronic alcohol exposure on phosphodiesterase-4B, an indirect biomarker of cAMP activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Article
  16. A Comparative Study of the Antiemetic Effects of αInternational journal of molecular sciences · 2024
    Article
  17. Review
  18. Article
  19. Article
  20. Article

15 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

4 authors at 3 institutions in 1 country.

Wito RichterUniversity of California San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA 94143-0556, USA. richterw@obgyn.ucsf.edu
Frank S Menniti
Han-Ting Zhang
Marco Conti
Weatherford College · USProvidence College · USWest Virginia University · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Phosphodiesterease-4 (PDE4) as a Novel Target to Reduce Ethanol ConsumptionR21AA020042 · NIAAA · WEST VIRGINIA UNIVERSITY · PI ZHANG, HAN-TING · 2011 to 2012
$389k
Targeting compartmentalized phosphodiesterases to regulate CFTR functionR21HL107960 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RICHTER, WITO H · 2012 to 2013
$377k
Gene silencing of phosphodiesterase-4D (PDE4D) as a therapeutic approach to beta R21AG031687 · NIA · WEST VIRGINIA UNIVERSITY · PI ZHANG, HAN-TING · 2008 to 2009
$320k
NHLBI NIH HHS HL107960NHLBI NIH HHS R21 HL107960NIAAA NIH HHS AA020042NIAAA NIH HHS R21 AA020042NIA NIH HHS AG031687NIA NIH HHS R21 AG031687NIDDK NIH HHS P30 DK072517
6 · The paper itself

Abstract

introductionThe second messengers cAMP and cGMP mediate fundamental aspects of brain function relevant to memory, learning, and cognitive functions. Consequently, cyclic nucleotide phosphodiesterases (PDEs), the enzymes that inactivate the cyclic nucleotides, are promising targets for the development of cognition-enhancing drugs. AREAS COVERED: PDE4 is the largest of the 11 mammalian PDE families. This review covers the properties and functions of the PDE4 family, highlighting procognitive and memory-enhancing effects associated with their inactivation. EXPERT OPINION: PAN-selective PDE4 inhibitors exert a number of memory- and cognition-enhancing effects and have neuroprotective and neuroregenerative properties in preclinical models. The major hurdle for their clinical application is to target inhibitors to specific PDE4 isoforms relevant to particular cognitive disorders to realize the therapeutic potential while avoiding side effects, in particular emesis and nausea. The PDE4 family comprises four genes, PDE4A-D, each expressed as multiple variants. Progress to date stems from characterization of rodent models with selective ablation of individual PDE4 subtypes, revealing that individual subtypes exert unique and non-redundant functions in the brain. Thus, targeting specific PDE4 subtypes, as well as splicing variants or conformational states, represents a promising strategy to separate the therapeutic benefits from the side effects of PAN-PDE4 inhibitors.

Indexed as

AnimalsCognitionCyclic Nucleotide Phosphodiesterases, Type 4HumansMemoryPhosphodiesterase 4 InhibitorsCyclic Nucleotide Phosphodiesterases, Type 4Phosphodiesterase 4 Inhibitors

Identifiers

PMID23883342
PMCPMC4066988
OpenAlexW2074422008

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.