Related Experiment Video

Updated: Mar 7, 2026

Modeling Age-Associated Neurodegenerative Diseases in Caenorhabditis elegans
07:04

Modeling Age-Associated Neurodegenerative Diseases in Caenorhabditis elegans

Published on: August 15, 2020

5.9K

Calcium Signaling and Pathogenesis of Neurodegenerative Disorders: Potential Therapeutic Opportunities

Ilya Bezprozvanny1,2,3

  • 1Laboratory of Molecular Neurobiology, Pavlov Institute of Physiology Russian Academy of Sciences, Saint Petersburg 199034, Russia mnlabspb@gmail.com bezprozvannyib@infran.ru.

Cold Spring Harbor Perspectives in Biology
|March 5, 2026
PubMed

Insights

The amyloid pathway has failed to treat neurodegenerative diseases. Exploring the calcium hypothesis, particularly with SERCA pump modulators, offers new therapeutic targets for Alzheimer's and similar disorders.

Area of Science:

  • Neuroscience
  • Pharmacology

Background:

  • Alzheimer's disease and other neurodegenerative disorders represent significant health and economic burdens.
  • Current therapeutic strategies primarily target the amyloid pathway, but have not resulted in effective disease-modifying treatments.

Purpose of the Study:

  • To review evidence supporting the "calcium hypothesis of neurodegeneration" as an alternative therapeutic avenue.
  • To address the clinical translation challenges of calcium signaling modulation.

Main Methods:

  • Review of existing literature on the calcium hypothesis of neurodegeneration.
  • Discussion of potential therapeutic agents, including positive allosteric modulators of the sarco-endoplasmic reticulum calcium (SERCA) pump.

Main Results:

  • The amyloid pathway has shown limited success in treating neurodegenerative diseases.
  • Concerns regarding side effects of traditional calcium channel blockers hinder clinical application.
  • Positive allosteric modulators of SERCA pumps present a potential solution to mitigate side effects.

Conclusions:

  • The calcium hypothesis offers promising alternative targets for neurodegenerative disorders.
  • SERCA pump modulators may overcome previous safety concerns, offering new therapeutic leads.
  • Further clinical trials are necessary to validate the safety and efficacy of SERCA modulators in humans.

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