Evidence map›Paper›PMID 34298984›Full record

ArticleInternational journal of molecular sciences2021

Norepinephrine May Oppose Other Neuromodulators to Impact Alzheimer's Disease.

Paul J Fitzgerald

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 37% 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

4 citing papers in PubMed, 10 citations in OpenAlex.

  1. The Contribution of the Locus Ceruleus-Norepinephrine System to the Coupling between Pupil-Linked Arousal and Cortical State.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  2. Article
  3. Review
  4. 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

1 author at 1 institution in 1 country.

Paul J FitzgeraldDepartment of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA.ORCID 0000-0002-5216-2189
University of Michigan · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

While much of biomedical research since the middle of the twentieth century has focused on molecular pathways inside the cell, there is increasing evidence that extracellular signaling pathways are also critically important in health and disease. The neuromodulators norepinephrine (NE), serotonin (5-hydroxytryptamine, 5HT), dopamine (DA), acetylcholine (ACH), and melatonin (MT) are extracellular signaling molecules that are distributed throughout the brain and modulate many disease processes. The effects of these five neuromodulators on Alzheimer's disease (AD) are briefly examined in this paper, and it is hypothesized that each of the five molecules has a u-shaped (or Janus-faced) dose-response curve, wherein too little or too much signaling is pathological in AD and possibly other diseases. In particular it is suggested that NE is largely functionally opposed to 5HT, ACH, MT, and possibly DA in AD. In this scenario, physiological "balance" between the noradrenergic tone and that of the other three or four modulators is most healthy. If NE is largely functionally opposed to other prominent neuromodulators in AD, this may suggest novel combinations of pharmacological agents to counteract this disease. It is also suggested that the

Indexed as

Adrenergic AgentsAdrenergic NeuronsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrain ChemistryCholinesterase InhibitorsDisease Models, AnimalDose-Response Relationship, DrugDrug SynergismHumansMelatoninMiceModels, NeurologicalNeurotransmitter AgentsNootropic AgentsAdrenergic AgentsAmyloid beta-PeptidesCholinesterase InhibitorsMelatoninNeurotransmitter AgentsNootropic AgentsNorepinephrineReceptors, Adrenergic, alpha-2Selective Serotonin Reuptake Inhibitorstau Proteinscholinesterase inhibitorsclonidinecognitive impairmentdementiaguanfacinelocus coeruleusneurodegenerationnoradrenalineprazosinpropranololterazosin

Identifiers

PMID34298984
PMCPMC8304567
OpenAlexW3178694233

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.