Dysregulation of Intracellular Calcium Signaling in Alzheimer's Disease

Elena Popugaeva, Ekaterina Pchitskaya, Ilya Bezprozvanny

Research output: Contribution to journalReview article

9 Scopus citations

Abstract

Significance: Calcium (Ca2+) hypothesis of Alzheimer's disease (AD) gains popularity. It points to new signaling pathways that may underlie AD pathogenesis. Based on calcium hypothesis, novel targets for the development of potential AD therapies are identified. Recent Advances: Recently, the key role of neuronal store-operated calcium entry (nSOCE) in the development of AD has been described. Correct regulation of nSOCE is necessary for the stability of postsynaptic contacts to preserve the memory formation. Molecular identity of hippocampal nSOCE is defined. Perspective nSOCE-activating molecule, prototype of future anti-AD drugs, is described. Critical Issues: Endoplasmic reticulum Ca2+ overload happens in many but not in all AD models. The nSOCE targeting therapy described in this review may not be universally applicable. Future Directions: There is a need to determine whether AD is a syndrome with one critical signaling pathway that initiates pathology, or it is a disorder with many different signaling pathways that are disrupted simultaneously or one after each other. It is necessary to validate applicability of nSOCE-activating therapy for the development of anti-AD medication. There is an experimental correlation between downregulated nSOCE and disrupted postsynaptic contacts in AD mouse models. Signaling mechanisms downstream of nSOCE which are responsible for the regulation of stability of postsynaptic contacts have to be discovered. That will bring new targets for the development of AD-preventing therapies. Antioxid. Redox Signal. 29, 1176-1188.

Original languageEnglish (US)
Pages (from-to)1176-1188
Number of pages13
JournalAntioxidants and Redox Signaling
Volume29
Issue number12
DOIs
StatePublished - Oct 20 2018

Keywords

  • Alzheimer's disease
  • ER calcium overload
  • nSOCE

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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