Evidence map›Paper›PMID 30092810›Full record

ArticleMolecular neurodegeneration2018

Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating α-synuclein transmission and neuroinflammation.

Changyoun Kim, Brian Spencer, Edward Rockenstein, Hodaka Yamakado, Michael Mante, Anthony Adame, Jerel Adam Fields, Deborah Masliah, Michiyo Iba, He-Jin Lee and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 1 pooled it
10.7field-weighted citation impact, top 1% of its field
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

102 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.

  1. Pooled it
  2. Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
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  15. Innate and adaptive immunity in neurodegenerative disease.Cellular and molecular life sciences : CMLS · 2025
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42 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 2 countries.

Changyoun KimMolecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
Brian SpencerDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Edward RockensteinDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Hodaka YamakadoDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Michael ManteDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Anthony AdameDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Jerel Adam FieldsDepartment of Pathology, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Deborah MasliahDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Michiyo IbaMolecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
He-Jin LeeDepartment of Anatomy, School of Medicine, Konkuk University, Seoul, 05029, Korea.
Robert A RissmanDepartment Neurosciences, School of Medicine, University of California, La Jolla, San Diego, CA, 92093, USA.
Seung-Jae LeeDepartment of Biomedical Sciences, Neuroscience Research Institute, and Department of Medicine, Seoul National University College of Medicine, Seoul, 03080, Korea. sjlee66@snu.ac.kr.
Eliezer MasliahMolecular Neuropathology Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA. eliezer.masliah@nih.gov.
University of California, San Diego · USNational Institute on Aging · USKonkuk University · KRSeoul National University · KR

Funding

Neuroimmune responses and therapeutics of alpha-synucleinopathies of the aging populationZIAAG000936 · NIA · NATIONAL INSTITUTE ON AGING · PI COOKSON, MARK · 2017 to 2025
$4.1M
Mitochondrial biogenesis dysfunction in the CNS of HIV-infected individuals on antiretroviral therapyK01MH115819 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIELDS, JEREL ADAM · 2018 to 2020
$480k
Pathogenicity of neuronally-derived tau in exosomesR21AG051839 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2016 to 2017
$426k
Polytherapy for AD: Combining Gamma-secretase Modulation and CRFR1 AntagonismR21AG047484 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT, WAGNER, STEVEN LEE · 2014 to 2015
$419k
Validation Studies of CRF Receptor 1 as a Target for ADI01BX003040 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI RISSMAN, ROBERT · 2016 to 2020
–
BLRD VA I01 BX003040NIA NIH HHS R21 AG047484NIA NIH HHS R21 AG051839NIMH NIH HHS K01 MH115819
6 · The paper itself

Abstract

backgroundSynucleinopathies of the aging population are an heterogeneous group of neurological disorders that includes Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and are characterized by the progressive accumulation of α-synuclein in neuronal and glial cells. Toll-like receptor 2 (TLR2), a pattern recognition immune receptor, has been implicated in the pathogenesis of synucleinopathies because TLR2 is elevated in the brains of patients with PD and TLR2 is a mediator of the neurotoxic and pro-inflammatory effects of extracellular α-synuclein aggregates. Therefore, blocking TLR2 might alleviate α-synuclein pathological and functional effects. For this purpose, herein, we targeted TLR2 using a functional inhibitory antibody (anti-TLR2).

methodsTwo different human α-synuclein overexpressing transgenic mice were used in this study. α-synuclein low expresser mouse (α-syn-tg, under the PDGFβ promoter, D line) was stereotaxically injected with TLR2 overexpressing lentivirus to demonstrate that increment of TLR2 expression triggers neurotoxicity and neuroinflammation. α-synuclein high expresser mouse (α-Syn-tg; under mThy1 promoter, Line 61) was administrated with anti-TLR2 to examine that functional inhibition of TLR2 ameliorates neuropathology and behavioral defect in the synucleinopathy animal model. In vitro α-synuclein transmission live cell monitoring system was used to evaluate the role of TLR2 in α-synuclein cell-to-cell transmission.

resultsWe demonstrated that administration of anti-TLR2 alleviated α-synuclein accumulation in neuronal and astroglial cells, neuroinflammation, neurodegeneration, and behavioral deficits in an α-synuclein tg mouse model of PD/DLB. Moreover, in vitro studies with neuronal and astroglial cells showed that the neuroprotective effects of anti-TLR2 antibody were mediated by blocking the neuron-to-neuron and neuron-to-astrocyte α-synuclein transmission which otherwise promotes NFκB dependent pro-inflammatory responses.

conclusionThis study proposes TLR2 immunotherapy as a novel therapeutic strategy for synucleinopathies of the aging population.

Indexed as

alpha-SynucleinAnimalsBrainDisease Models, AnimalHumansImmunotherapyLewy Body DiseaseMiceMice, TransgenicNerve DegenerationParkinsonian DisordersToll-Like Receptor 2alpha-SynucleinSNCA protein, humanToll-Like Receptor 2ImmunotherapyNeurodegenerationNeuroinflammationParkinson’s diseaseSynucleinopathyToll-like receptor 2Transmissionα-synuclein

Identifiers

PMID30092810
PMCPMC6085656
OpenAlexW2887383740

What OpenQuestion holds

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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.