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Cited by 66Ion Transport and Channel RegulationATP Synthase and ATPases ResearchAlzheimer's disease research and treatments

Recent advances in the study of Na+/K+-ATPase in neurodegenerative diseases

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Zhang, Xiaoyan, Lee, Weithye, Bian, Jin-Song·2022·Cells
DOI 10.3390/cells11244075PMC PMC9777075
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Abstract

Na+/K+-ATPase (NKA), a large transmembrane protein, is expressed in the plasma membrane of most eukaryotic cells. It maintains resting membrane potential, cell volume and secondary transcellular transport of other ions and neurotransmitters. NKA consumes about half of the ATP molecules in the brain, which makes NKA highly sensitive to energy deficiency. Neurodegenerative diseases (NDDs) are a group of diseases characterized by chronic, progressive and irreversible neuronal loss in specific brain areas. The pathogenesis of NDDs is sophisticated, involving protein misfolding and aggregation, mitochondrial dysfunction and oxidative stress. The protective effect of NKA against NDDs has been emerging gradually in the past few decades. Hence, understanding the role of NKA in NDDs is critical for elucidating the underlying pathophysiology of NDDs and identifying new therapeutic targets. The present review focuses on the recent progress involving different aspects of NKA in cellular homeostasis to present in-depth understanding of this unique protein. Moreover, the essential roles of NKA in NDDs are discussed to provide a platform and bright future for the improvement of clinical research in NDDs.

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  • Loss-of-function mutations in all three CNS α subunits cause epilepsy.

    “Loss-of-function mutations in all three CNS α subunits cause epilepsy (Zhang et al., 2022)”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Zhang et al., 2022

    Section 2.2 (page unavailable) says α2 mutations can cause epilepsy, and the References list links ATP1A3 (α3) mutations with early-life epilepsy. But section 2.2 describes α1 mutations as fatal, not as causing epilepsy, and the copy does not establish that the epilepsy-associated mutations in all three isoforms are loss-of-function. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Decreased expression and function of Na+/K+-ATPase is associated with hyperexcitability disorders including epilepsy, migraine, dystonia-parkinsonism, and AD.

    “Decreased expression and function of Na+/K+-ATPase is associated with hyperexcitability disorders including epilepsy, migraine, dystonia-parkinsonism, and AD (Sun et al., 2022; Zhang et al., 2022).”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Zhang et al., 2022

    Section 2.2 links Na+/K+-ATPase subunit mutations to epilepsy, hemiplegic migraine, and rapid-onset dystonia-parkinsonism. Section 3 reports reduced ATPase activity in AD patients and rodent models, and reduced expression in an AD rodent model. The paper does not establish decreased expression and function across all four conditions or classify them all as hyperexcitability disorders. Page numbers were not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • ATP hydrolysis is essential for Na+/K+-ATPase to transport 3 Na+ out of the cell and 2 K+ into the cell.

    “ATP hydrolysis is essential for Na+/K+-ATPase to transport 3 Na+ out of the cell and 2 K+ into the cell (Sun et al., 2022; Zhang et al., 2022).”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Zhang et al., 2022

    Section 2.1 identifies Na+/K+-ATPase as a sodium pump, section 2.2 describes its ATP-binding catalytic subunit, and section 2.3 says it modulates Na+ and K+ gradients. Our copy does not specify that it transports three Na+ out for every two K+ in, or explicitly link that transport cycle to ATP hydrolysis. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • APOE4-induced decline in ATP production and Na+/K+-ATPase α1 expression will collectively reduce the activity of Na+/K+-ATPase critical for maintaining RMP and neuronal excitability especially during energetically demanding processes such as seizures.

    “In addition, APOE4-induced decline in ATP production (Fig. 4C, J) and Na+/K+-ATPase α1 expression (Fig. 3A-E) will collectively reduce the activity of Na+/K+-ATPase critical for maintaining RMP and neuronal excitability (Fig. 3F-J) (Sun et al., 2022; Zhang et al., 2022) especially during energetically demanding processes such as seizures (Meyer et al., 2022) (Fig. 6).”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Zhang et al., 2022

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Na+/K+-ATPase α1 establishes and maintains electrochemical gradients of Na+ and K+ ions across the plasma membrane.

    “the Na+/K+-ATPase α1 establishes and maintains electrochemical gradients of Na+ and K+ ions across the plasma membrane (Sun et al., 2022; Zhang et al., 2022)”

    From APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice (2026) · cites this paper as Zhang et al., 2022

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Cited by

Sorted by citations

Authors
Zhang, X., Lee, W., & Bian, J.-S.
Affiliations
  • Southern University of Science and Technology (CN)
  • National University of Singapore (SG)
Corresponding author
Bian, Jin-Song
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2022-12-16
Volume
11
Issue
24
Pages
4075
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells11244075
PMC
PMC9777075
OpenAlex
W4312195912
Cited by
66
References
1
Citations by year
2026: 11 · 2025: 19 · 2024: 32 · 2023: 4
FWCI
1.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (NSFC) (82173800, 81872865, KQTD20200820113040070)
  • henzhen Science and Technology Program (82173800, 81872865, KQTD20200820113040070)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Na+/K+-ATPase, neurodegenerative diseases, resting membrane potential, cell volume regulation, energy deficiency, mitochondrial dysfunction, oxidative stress, neuroprotection, therapeutic target
MeSH terms
Sodium-Potassium-Exchanging ATPase, Humans, Ions, Membrane Potentials, Sodium, Neurodegenerative Diseases

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