Evidence map›Paper›PMID 21925266›Full record

ReviewBiochimica et biophysica acta2011

Calcium channel blocking as a therapeutic strategy for Alzheimer's disease: the case for isradipine.

Thimmappa S Anekonda, Joseph F Quinn

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Amyloid β alters vascular CaThe Journal of physiology · 2025
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  19. L-Type CaInternational journal of molecular sciences · 2022
    Article
  20. Article

13 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

2 authors at 1 institution in 1 country.

Thimmappa S AnekondaDepartment of Neurology, Oregon Health and Science University, Portland, OR, USA. anekondt@ohsu.edu
Joseph F Quinn
Oregon Health & Science University · US

Funding

Treatment of autoimmune retinopathies with anti-aging polyphenol resveratrolR21EY018708 · NEI · OREGON HEALTH & SCIENCE UNIVERSITY · PI ANEKONDA, THIMMAPPA S · 2009 to 2010
$423k
Copper Complexing with Tetrathiomolybdate in a Murine Model of Alzheimers DiseaseR21AG027445 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI QUINN, JOSEPH F · 2006 to 2007
$302k
NEI NIH HHS 5R21EY018708-02NEI NIH HHS R21 EY018708NIA NIH HHS R21 AG027445PHS HHS R21SG027445A
6 · The paper itself

Abstract

Alzheimer's disease is the most devastating neurodegenerative disorder in the elderly, yet treatment options are severely limited. The drug development effort to modify Alzheimer's disease pathology by intervention at beta amyloid production sites has been largely ineffective or inconclusive. The greatest challenge has been to identify and define downstream mechanisms reliably predictive of clinical symptoms. Beta amyloid accumulation leads to dysregulation of intracellular calcium by plasma membrane L-type calcium channels located on neuronal somatodendrites and axons in the hippocampus and cortex. Paradoxically, L-type calcium channel subtype Ca(v)1.2 also promotes synaptic plasticity and spatial memory. Increased intracellular calcium modulates amyloid precursor protein processing and affects multiple downstream pathways including increased hyperphosphorylated tau and suppression of autophagy. Isradipine is a Federal Drug Administration-approved dihydropyridine calcium channel blocker that binds selectively to Ca(v)1.2 in the hippocampus. Our studies have shown that isradipine in vitro attenuates beta amyloid oligomer toxicity by suppressing calcium influx into cytoplasm and by suppressing Ca(v)1.2 expression. We have previously shown that administration of isradipine to triple transgenic animal model for Alzheimer's disease was well-tolerated. Our results further suggest that isradipine became bioavailable, lowered tau burden, and improved autophagy function in the brain. A better understanding of brain pharmacokinetics of calcium channel blockers will be critical for designing new experiments with appropriate drug doses in any future clinical trials for Alzheimer's disease. This review highlights the importance of Ca(v)1.2 channel overexpression, the accumulation of hyperphosphorylated tau and suppression of autophagy in Alzheimer's disease and modulation of this pathway by isradipine.

Indexed as

Alzheimer DiseaseAnimalsAutophagyCalciumCalcium Channel BlockersCalcium Channels, L-TypeHumansIsradipinetau ProteinsCalciumCalcium Channel BlockersCalcium Channels, L-TypeIsradipinetau Proteins

Identifiers

PMID21925266
PMCPMC3275089
OpenAlexW2144987307

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.