Evidence map›Paper›PMID 26088971›Full record

ArticleCerebral cortex (New York, N.Y. : 1991)2016

Cdk5 is a New Rapid Synaptic Homeostasis Regulator Capable of Initiating the Early Alzheimer-Like Pathology.

Yanghui Sheng, Lei Zhang, Susan C Su, Li-Huei Tsai, J Julius Zhu

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cerebral cortex (New York, N.Y. : 1991), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.5field-weighted citation impact, top 19% 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

18 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Advances in the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Role of Aβ in Alzheimer's-related synaptic dysfunction.Frontiers in cell and developmental biology · 2022
    Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. CDK5 downregulation enhances synaptic plasticity.Cellular and molecular life sciences : CMLS · 2017
    Article
  16. Article
  17. Review
  18. Article
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

5 authors at 3 institutions in 2 countries.

Yanghui ShengDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA Undergraduate Class of 2011, Yuanpei Honors College, Peking University, Beijing 100871, China Current address: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lei ZhangDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Susan C SuPicower Institute for Learning and Memory and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Li-Huei TsaiPicower Institute for Learning and Memory and Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Julius ZhuDepartment of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Howard Hughes Medical Institute · USUniversity of Virginia · USPeking University · CN

Funding

Calcium channel and glutamate receptor signaling at synapsesR01NS091452 · NINDS · UNIVERSITY OF VIRGINIA · PI ZHU, J. JULIUS · 2015 to 2019
$1.7M
Synaptic Depression: Focus on Cdk5 SignalingR01NS092548 · NINDS · UNIVERSITY OF VIRGINIA · PI ZHU, J. JULIUS · 2015 to 2019
$1.7M
Interneuron-based cell therapy for Fragile XR21NS094980 · NINDS · UNIVERSITY OF VIRGINIA · PI ZHU, J. JULIUS · 2016 to 2017
$431k
Howard Hughes Medical InstituteNINDS NIH HHS R01 NS091452NINDS NIH HHS R01 NS092548NINDS NIH HHS R21 NS094980
6 · The paper itself

Abstract

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase implicated in synaptic plasticity, behavior, and cognition, yet its synaptic function remains poorly understood. Here, we report that physiological Cdk5 signaling in rat hippocampal CA1 neurons regulates homeostatic synaptic transmission using an unexpectedly rapid mechanism that is different from all known slow homeostatic regulators, such as beta amyloid (Aβ) and activity-regulated cytoskeleton-associated protein (Arc, aka Arg3.1). Interestingly, overproduction of the potent Cdk5 activator p25 reduces synapse density, and dynamically regulates synaptic size by suppressing or enhancing Aβ/Arc production. Moreover, chronic overproduction of p25, seen in Alzheimer's patients, induces initially concurrent reduction in synapse density and increase in synaptic size characteristic of the early Alzheimer-like pathology, and later persistent synapse elimination in intact brains. These results identify Cdk5 as the regulator of a novel rapid form of homeostasis at central synapses and p25 as the first molecule capable of initiating the early Alzheimer's synaptic pathology.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCA1 Region, HippocampalCells, CulturedCyclin-Dependent Kinase 5Cytoskeletal ProteinsDisease Models, AnimalFemaleHomeostasisMaleMicroscopy, ElectronNerve Tissue ProteinsNeuronal PlasticityPatch-Clamp TechniquesPhosphotransferasesactivity regulated cytoskeletal-associated proteinAmyloid beta-PeptidesCdk5 protein, ratCdk5r1 protein, ratCyclin-Dependent Kinase 5Cytoskeletal ProteinsNerve Tissue ProteinsPhosphotransferasesCdk5cortexhippocampusneurodegenerative diseasessynaptic depressionsynaptic homeostasis

Identifiers

PMID26088971
PMCPMC4898661
OpenAlexW2288728691

What OpenQuestion holds

Textmetadata
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.