Presenilins and calcium signaling - Systems biology to the rescue

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Mutations in presenilins result in familial Alzheimer's disease (FAD). Presenilins encode a catalytic subunit of the γ-secretase complex, and FAD mutations in presenil-ins alter γ-secretase activity. Many FAD mutations in presenilins also affect intracel-lular calcium signaling. To explain these results, it was proposed that presenilins also function as endoplasmic reticulum (ER) calcium leak channels and that this function is disrupted by FAD mutations. Although this hypothesis has been controversial, new research supports the calcium leak channel hypothesis. One group reported the presence of putative ion-conduction pore in the high-resolution crystal structure of bacterial presenilin homolog PSH1. Another group identifi ed an essential role for presenilins in mediating ER calcium leak in a cell-based screen for calcium homeostasis modulators. These results should enable the fi eld to move forward and to focus on exploring connections between FAD mutations in presenilins, changes in γ-secretase and ER Ca2+ leak functions, and development of the disease.

Original languageEnglish (US)
Article numberpe24
JournalScience Signaling
Volume6
Issue number283
DOIs
StatePublished - Jul 9 2013

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Presenilins
Systems Biology
Calcium Signaling
Calcium
Alzheimer Disease
Amyloid Precursor Protein Secretases
Mutation
Endoplasmic Reticulum
Calcium Channels
Bacterial Structures
Modulators
Catalytic Domain
Homeostasis
Crystal structure
Ions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Presenilins and calcium signaling - Systems biology to the rescue. / Bezprozvanny, Ilya.

In: Science Signaling, Vol. 6, No. 283, pe24, 09.07.2013.

Research output: Contribution to journalArticle

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