Evidence map›Paper›PMID 38293195›Full record

ArticlebioRxiv : the preprint server for biology2024

Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson's disease.

Shahzad S Khan, Ebsy Jaimon, Yu-En Lin, Jonas Nikoloff, Francesca Tonelli, Dario R Alessi, Suzanne R Pfeffer

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Shahzad S KhanDepartment of Biochemistry, Stanford University School of Medicine, United States.ORCID 0000-0003-3962-0226
Ebsy JaimonDepartment of Biochemistry, Stanford University School of Medicine, United States.ORCID 0000-0001-6845-2095
Yu-En LinDepartment of Biochemistry, Stanford University School of Medicine, United States.ORCID 0000-0002-5848-5405
Jonas NikoloffDepartment of Biochemistry, Stanford University School of Medicine, United States.ORCID 0000-0002-7823-454X
Francesca TonelliAligning Science Across Parkinson's (ASAP) Collaborative Research Network, United States.ORCID 0000-0002-4600-6630
Dario R AlessiAligning Science Across Parkinson's (ASAP) Collaborative Research Network, United States.ORCID 0000-0002-2140-9185
Suzanne R PfefferDepartment of Biochemistry, Stanford University School of Medicine, United States.ORCID 0000-0002-6462-984X

Funding

Supplement to Enhance Wellness and Resiliency in the Graduate EnvironmentT32GM007276 · NIGMS · STANFORD UNIVERSITY · PI MORRISON, ASHBY J. · 1985 to 2023
$32.9M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI ALIREZA ATRI · 2021 to 2026
$24.9M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072980NIGMS NIH HHS T32 GM007276NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

Activating LRRK2 mutations cause Parkinson's disease. Previously, we showed that cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2 mutant mice. Single nucleus RNA sequencing shows that cilia loss in cholinergic interneurons correlates with higher LRRK2 expression and decreased glial derived neurotrophic factor transcription. Nevertheless, much higher LRRK2 expression is seen in medium spiny neurons that have normal cilia in mice and humans. In parallel with decreased striatal dopaminergic neurite density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion protein expression; glial cells show significant loss of ferritin heavy chain. Human striatal tissue from LRRK2 pathway mutation carriers and idiopathic Parkinson's disease show similar cilia loss in cholinergic interneurons and astrocytes and overall loss of such neurons. These data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson's disease.

Identifiers

PMID38293195
PMCPMC10827083

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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.