Linoleic acid improves PIEZO2 dysfunction in a mouse model of Angelman Syndrome
Romero LO, Caires R, Kaitlyn Victor A, Ramirez J, Sierra-Valdez FJ, Walsh P, Truong V, Lee J, Mayor U, Reiter LT, Vásquez V, Cordero-Morales JF
Nature communications · 71 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Foundation for Prader-Willi Research
- University or hospital
- Wayne State University
- Government
- National Institutes of Health
- Government
- National Institute of General Medical Sciences
- Government
- National Center for Research Resources
- University or hospital
- Federico Baur endowed chair in Nanotechnology
- Government
- NCRR NIH HHS
- Government
- NIGMS NIH HHS
- Grants
- National Center for Research Resources (S10-RR-027926); National Institute of General Medical Sciences (R01GM133845); National Institutes of Health (1s10rr027926-01); National Institutes of Health (R01GM133845); National Institutes of Health (R01 GM125629); National Institute of General Medical Sciences (R01 GM125629)
Based on 8 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2023-03-01 · Nat Commun · vol. 14 · issue 1 · p. 1167
- Publisher
- Nature Portfolio
- Cited
- 63 citations · more than 99% of similar papers · 12.5× the field average
- Impact
- Top 10% most cited in its field
- References
- 110 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genetic Syndromes and Imprinting · Erythrocyte Function and Pathophysiology · Ion channel regulation and function
- Keywords
- UBE3A, Angelman syndrome, Biology, Ubiquitin ligase, Neurodevelopmental disorder, Cell biology, Neuroscience, Genetics, Ubiquitin, Gene
- MeSH
- animals, humans, mice, angelman syndrome, disease models, animal, ubiquitin-protein ligases, linoleic acid, ion channels, alleles, female, male, intellectual disability
12 authors
From US, ES, MX
- Luis O. RomeroUniversity of Tennessee Health Science Center
- Rebeca CairesUniversity of Tennessee Health Science Center
- A. Kaitlyn VictorUniversity of Tennessee Health Science Center
- Juanma RamírezUniversity of the Basque Country
- Francisco J. Sierra-ValdezTecnológico de Monterrey
- Patrick WalshMidwest Orthopaedic Research Foundation
Abstract
Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss of UBE3A decreases actin filaments and reduces PIEZO2 expression and function. A linoleic acid (LA)-enriched diet increases PIEZO2 activity, mechano-excitability, and improves gait in male AS mice. Finally, LA supplementation increases PIEZO2 function in stem cell-derived neurons from individuals with AS. We propose a mechanism whereby loss of UBE3A expression reduces PIEZO2 function and identified a fatty acid that enhances channel activity and ameliorates AS-associated mechano-sensory deficits.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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