Evidence map›Paper›PMID 41981240›Full record

Articlenpj metabolic health and disease2026

Lipid membrane remodeling by myristic acid treatment reverses Parkinson's disease α-synuclein phenotypes in patient neurons.

Julian Avila Pacheco, Gleidia Sauli, Luis Fonseca-Ornelas, Haley Cirka, Deepa Kumari, Morgan Hazo, Sarah Jeanfavre, Pedro H Vendramini, Christina R Muratore, Clary B Clish and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in npj metabolic health and disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Julian Avila PachecoBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Gleidia SauliAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Luis Fonseca-OrnelasAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Haley CirkaAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Deepa KumariAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Morgan HazoAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Sarah JeanfavreBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Pedro H VendraminiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Christina R MuratoreAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Clary B ClishBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Dennis SelkoeAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Saranna FanningAnn Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. sfanning2@bwh.harvard.edu.

Funding

Mechanistic Dissection of Lipase (LIPE) Regulation of Fatty Acid Homeostasis as a Parkinson's Disease and Lewy Body Dementia Therapeutic StrategyR01NS133243 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Saranna Fanning · 2024 to 2026
$2.1M
Biology of Native Alpha-Synuclein Tetramers in Parkinson's DiseaseR01NS083845 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SELKOE, DENNIS J · 2014 to 2018
$1.8M
NIH HHS R01 NS083845NIH HHS R01 NS133243
6 · The paper itself

Abstract

Despite the lipid-rich nature of the brain, defining the role of lipid metabolism in neurodegenerative disease and targeting lipid metabolic pathways for disease modification are in their infancy. In Parkinson's disease, Lewy body dementia, and other synucleinopathies, disease-associated forms of α-synuclein (αS) alter fatty acid (FA) metabolism, increasing monounsaturated FA-containing lipids. This disequilibrium in membrane fatty acyl composition results in aberrant αS:membrane interactions. We report treating PD patient neurons with myristic acid (C14:0) induces lipid metabolism modifications correcting abnormal PD-associated membrane composition and reversing PD-relevant phenotypes. C14:0 conditioning reduced Lewy-like αS inclusions; reduced abnormal pSer129 αS; corrected excess αS at membranes; and restored native αS tetramer:monomer homeostasis. Using nuclear magnetic resonance, we established C14:0 as correcting abnormal αS vesicle membranes dwell time in vitro, correlating with less pathogenic αS aggregation. Mechanistically, C14:0 rescued PD neuron phenotypes through remodeling the PD-associated lipidome, eliciting beneficial effects by increasing shorter, saturated fatty acyl-lipids.

Identifiers

PMID41981240
PMCPMC13079797

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.