Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease

Elena Popugaeva, Ilya Bezprozvanny

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Alzheimer disease (AD) is a major threat of twenty-first century that is responsible for the majority of dementia in the elderly. Development of effective AD-preventing therapies are the top priority tasks for neuroscience research. Amyloid hypothesis of AD is a dominant idea in the field, but so far all amyloid-targeting therapies have failed in clinical trials. In addition to amyloid accumulation, there are consistent reports of abnormal calcium signaling in AD neurons. AD neurons exhibit enhanced intracellular calcium (Ca2+) liberation from the endoplasmic reticulum (ER) and reduced store-operated Ca2+ entry (SOC). These changes occur primarily as a result of ER Ca2+ overload. We argue that normalization of intracellular Ca2+ homeostasis could be a strategy for development of effective disease-modifying therapies. The current review summarizes recent data about changes in ER Ca2+ signaling in AD. Ca2+ channels that are discussed in the current review include: inositol trisphosphate receptors, ryanodine receptors, presenilins as ER Ca2+ leak channels, and neuronal SOC channels. We discuss how function of these channels is altered in AD and how important are resulting Ca2+ signaling changes for AD pathogenesis.

Original languageEnglish (US)
Article number29
JournalFrontiers in Molecular Neuroscience
Volume6
Issue numberSEP
DOIs
StatePublished - Sep 18 2013

Fingerprint

Endoplasmic Reticulum
Alzheimer Disease
Amyloid
Presenilins
Neurons
Ryanodine Receptor Calcium Release Channel
Calcium Signaling
Inositol
Neurosciences
Dementia
Homeostasis
Therapeutics
Clinical Trials
Calcium
Research

Keywords

  • Alzheimer disease
  • Ca signaling
  • Dantrolene
  • Endoplasmic reticulum
  • Inositol trisphosphate receptors
  • Presenilins
  • Ryanodine receptors
  • Store-operated Ca channels

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology

Cite this

Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease. / Popugaeva, Elena; Bezprozvanny, Ilya.

In: Frontiers in Molecular Neuroscience, Vol. 6, No. SEP, 29, 18.09.2013.

Research output: Contribution to journalArticle

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