Evidence for a role of plasma membrane calcium pumps in neurodegenerative disease: Recent developments

Emanuel E. Strehler, Stanley A. Thayer

Research output: Contribution to journalReview articlepeer-review

10 Scopus citations

Abstract

Plasma membrane Ca2+ ATPases (PMCAs) are a major system for calcium extrusion from all cells. Different PMCA isoforms and splice variants are involved in the precise temporal and spatial handling of Ca2+ signals and the re-establishment of resting Ca2+ levels in the nervous system. Lack or inappropriate expression of specific PMCAs leads to characteristic neuronal phenotypes, which may be reciprocally exacerbated by genetic predisposition through alleles in other genes that modify PMCA interactions, regulation, and function. PMCA dysfunction is often poorly compensated in neurons and may lead to changes in synaptic transmission, altered excitability and, with long-term calcium overload, eventual cell death. Decrease and functional decline of PMCAs are hallmarks of neurodegeneration during aging, and mutations in specific PMCAs are responsible for neuronal dysfunction and accelerated neurodegeneration in many sensory and cognitive diseases.

Original languageEnglish (US)
Pages (from-to)39-47
Number of pages9
JournalNeuroscience Letters
Volume663
DOIs
StatePublished - Jan 10 2018

Bibliographical note

Funding Information:
This work was funded by the National Institutes of Health [grant number DA07304 to SAT].

Publisher Copyright:
© 2017 Elsevier B.V.

Keywords

  • Calcium homeostasis
  • Cerebellar ataxia
  • Excitotoxicity
  • Neurodegenerative disease
  • Plasma membrane calcium ATPase

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