Evidence map›Paper›PMID 25307220›Full record

ReviewAdvances in pharmacology (San Diego, Calif.)2014

Delivery of therapeutic peptides and proteins to the CNS.

Therese S Salameh, William A Banks

Abstract readReview
In one paragraph

Review in Advances in pharmacology (San Diego, Calif.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

33 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
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  3. Review
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  10. Review
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  13. Transferrin Aptamers Increase theBioconjugate chemistry · 2022
    Article
  14. Review
  15. Review
  16. Review
  17. Drug Delivery Strategies to Overcome the Blood-Brain Barrier (BBB).Handbook of experimental pharmacology · 2022
    Article
  18. Review
  19. Article
  20. Review
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

2 authors at 2 institutions in 1 country.

Therese S SalamehGeriatric Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington USA; Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington, USA.
William A BanksGeriatric Research Educational and Clinical Center, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington USA; Department of Medicine, Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington, USA. Electronic address: wabanks1@uw.edu.
University of Puget Sound · USUniversity of Washington · US

Funding

NEUROBEHAVIOR, NEUROENDOCRINOLOGY, AND GENETICS OF ADT32AG000258 · NIA · UNIVERSITY OF WASHINGTON · PI MONTINE, THOMAS J · 1999 to 2013
$4.7M
Intranasal Insulin in a Mouse Model of Alzheimer's DiseaseR01AG046619 · NIA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI BANKS, WILLIAM A · 2014 to 2018
$2.4M
Oxidative Dysfunction of LRP at the Blood-brain Barrier in Alzheimer's DiseaseR01AG029839 · NIA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI BANKS, WILLIAM A · 2008 to 2012
$1.7M
NIA NIH HHS R01 AG029839NIA NIH HHS R01 AG046619NIA NIH HHS T32 AG000258NIA NIH HHS T32AG000258
6 · The paper itself

Abstract

Peptides and proteins have potent effects on the brain after their peripheral administration, suggesting that they may be good substrates for the development of CNS therapeutics. Major hurdles to such development include their relation to the blood-brain barrier (BBB) and poor pharmacokinetics. Some peptides cross the BBB by transendothelial diffusion and others cross in the blood-to-brain direction by saturable transporters. Some regulatory proteins are also transported across the BBB and antibodies can enter the CNS via the extracellular pathways. Glycoproteins and some antibody fragments can be taken up and cross the BBB by mechanisms related to adsorptive endocytosis/transcytosis. Many peptides and proteins are transported out of the CNS by saturable efflux systems and enzymatic activity in the blood, CNS, or BBB are substantial barriers to others. Both influx and efflux transporters are altered by various substances and in disease states. Strategies that manipulate these interactions between the BBB and peptides and proteins provide many opportunities for the development of therapeutics. Such strategies include increasing transendothelial diffusion of small peptides, upregulation of saturable influx transporters with allosteric regulators and other posttranslational means, use of vectors and other Trojan horse strategies, inhibition of efflux transporters including with antisense molecules, and improvement in pharmacokinetic parameters to overcome short half-lives, tissue sequestration, and enzymatic degradation.

Indexed as

AnimalsBlood-Brain BarrierHumansPeptidesProteinsPeptidesProteinsBlood–brain barrierCentral nervous systemDrug deliveryPeptidesProteinsTransport

Identifiers

PMID25307220
PMCPMC6087545
OpenAlexW2201269316

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.