Evidence map›Paper›PMID 38750146›Full record

ArticleCommunications biology2024

Sex-dependent interactions between prodromal intestinal inflammation and LRRK2 G2019S in mice promote endophenotypes of Parkinson's disease.

Ping Fang, Lewis W Yu, Hannah Espey, Gulistan Agirman, Sabeen A Kazmi, Kai Li, Yongning Deng, Jamie Lee, Haley Hrncir, Arlene Romero-Lopez and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. 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.

Ping FangDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA. phoen.f@gmail.com.ORCID 0000-0003-4379-3787
Lewis W YuDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Hannah EspeyDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Gulistan AgirmanDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Sabeen A KazmiDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID 0000-0002-3913-6170
Kai LiF. Widjaja Foundation Inflammatory Bowel & Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Yongning DengDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jamie LeeDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Haley HrncirDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Arlene Romero-LopezUCLA Goodman-Luskin Microbiome Center, Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, 90095, USA.ORCID 0009-0005-1141-713X
Arthur P ArnoldDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Elaine Y HsiaoDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, 90095, USA. ehsiao@g.ucla.edu.ORCID 0000-0002-1633-588X

Funding

Epigenetic regulation of myocardial ischemia/reperfusion injury by X chromosomeR01HL131182 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, EGHBALI, MANSOUREH · 2016 to 2019
$1.5M
NHLBI NIH HHS R01 HL131182U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) NIH HL131182
6 · The paper itself

Abstract

Gastrointestinal (GI) disruptions and inflammatory bowel disease (IBD) are commonly associated with Parkinson's disease (PD), but how they may impact risk for PD remains poorly understood. Herein, we provide evidence that prodromal intestinal inflammation expedites and exacerbates PD endophenotypes in rodent carriers of the human PD risk allele LRRK2 G2019S in a sex-dependent manner. Chronic intestinal damage in genetically predisposed male mice promotes α-synuclein aggregation in the substantia nigra, loss of dopaminergic neurons and motor impairment. This male bias is preserved in gonadectomized males, and similarly conferred by sex chromosomal complement in gonadal females expressing human LRRK2 G2019S. The early onset and heightened severity of neuropathological and behavioral outcomes in male LRRK2 G2019S mice is preceded by increases in α-synuclein in the colon, α-synuclein-positive macrophages in the colonic lamina propria, and loads of phosphorylated α-synuclein within microglia in the substantia nigra. Taken together, these data reveal that prodromal intestinal inflammation promotes the pathogenesis of PD endophenotypes in male carriers of LRRK2 G2019S, through mechanisms that depend on genotypic sex and involve early accumulation of α-synuclein in myeloid cells within the gut.

Indexed as

Leucine-Rich Repeat Serine-Threonine Protein Kinase-2Parkinson Diseasealpha-SynucleinAnimalsDisease Models, AnimalEndophenotypesFemaleHumansInflammationMaleMiceMice, Inbred C57BLMice, TransgenicProdromal SymptomsSex CharacteristicsSex Factorsalpha-SynucleinLeucine-Rich Repeat Serine-Threonine Protein Kinase-2

Identifiers

PMID38750146
PMCPMC11096388

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.