Evidence map›Paper›PMID 25071552›Full record

ReviewFrontiers in aging neuroscience2014

Copper: from neurotransmission to neuroproteostasis.

Carlos M Opazo, Mark A Greenough, Ashley I Bush

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in aging neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 157 citations in OpenAlex.

  1. Pooled it
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  6. Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025
    Review
  7. Review
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  9. A primer on copper biology in the brain.Neurobiology of disease · 2025
    Review
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23 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

3 authors at 2 institutions in 1 country.

Carlos M OpazoOxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne Melbourne, VIC, Australia.
Mark A GreenoughOxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne Melbourne, VIC, Australia.
Ashley I BushOxidation Biology Laboratory, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne Melbourne, VIC, Australia.
University of Melbourne · AUFlorey Institute of Neuroscience and Mental Health · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Copper is critical for the Central Nervous System (CNS) development and function. In particular, different studies have shown the effect of copper at brain synapses, where it inhibits Long Term Potentation (LTP) and receptor pharmacology. Paradoxically, according to recent studies copper is required for a normal LTP response. Copper is released at the synaptic cleft, where it blocks glutamate receptors, which explain its blocking effects on excitatory neurotransmission. Our results indicate that copper also enhances neurotransmission through the accumulation of PSD95 protein, which increase the levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors located at the plasma membrane of the post-synaptic density. Thus, our findings represent a novel mechanism for the action of copper, which may have implications for the neurophysiology and neuropathology of the CNS. These data indicate that synaptic configuration is sensitive to transient changes in transition metal homeostasis. Our results suggest that copper increases GluA1 subunit levels of the AMPA receptor through the anchorage of AMPA receptors to the plasma membrane as a result of PSD-95 accumulation. Here, we will review the role of copper on neurotransmission of CNS neurons. In addition, we will discuss the potential mechanisms by which copper could modulate neuronal proteostasis ("neuroproteostasis") in the CNS with focus in the Ubiquitin Proteasome System (UPS), which is particularly relevant to neurological disorders such as Alzheimer's disease (AD) where copper and protein dyshomeostasis may contribute to neurodegeneration. An understanding of these mechanisms may ultimately lead to the development of novel therapeutic approaches to control metal and synaptic alterations observed in AD patients.

Indexed as

AMPAcopperE-ligaseshippocampal neuronsneurotransmissionproteasomesynaptic activityubiquitination

Identifiers

PMID25071552
PMCPMC4080678
OpenAlexW2046200968

What OpenQuestion 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 OpenQuestion graph.