Evidence map›Paper›PMID 38370818›Full record

ArticlebioRxiv : the preprint server for biology2024

TPPB modulates PKC activity to attenuate neuroinflammation and ameliorate experimental multiple sclerosis.

Shruthi Shanmukha, Wesley H Godfrey, Payam Gharibani, Judy J Lee, Yu Guo, Xiaojing Deng, Paul A Wender, Michael D Kornberg, Paul M Kim

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
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, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Shruthi ShanmukhaDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Wesley H GodfreyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Payam GharibaniDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Judy J LeeDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Yu GuoDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine; Baltimore, Maryland, 21287, USA.
Xiaojing DengDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Paul A WenderDepartments of Chemistry and of Chemical and Systems Biology, Stanford University, Stanford, California, 94305, USA.
Michael D KornbergDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Paul M KimDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA.
Johns Hopkins University · USStanford University · US

Funding

Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
SYNTHETIC STUDIES RELATED TO CANCER RESEARCH/TREATMENTR01CA031845 · NCI · STANFORD UNIVERSITY · PI PAUL Anthony WENDER · 1985 to 2026
$6.9M
NCI NIH HHS R01 CA031845NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

Protein kinase C (PKC) plays a key role in modulating the activities of the innate immune cells of the central nervous system (CNS). A delicate balance between pro-inflammatory and regenerative activities by microglia and CNS-associated macrophages is necessary for the proper functioning of the CNS. Thus, a maladaptive activation of these CNS innate immune cells results in neurodegeneration and demyelination associated with various neurologic disorders, such as multiple sclerosis (MS) and Alzheimer's disease. Prior studies have demonstrated that modulation of PKC activity by bryostatin-1 (bryo-1) and its analogs (bryologs) attenuates the pro-inflammatory processes by microglia/CNS macrophages and alleviates the neurologic symptoms in experimental autoimmune encephalomyelitis (EAE), an MS animal model. Here, we demonstrate that (2S,5S)-(E,E)-8-(5-(4(trifluoromethyl)phenyl)-2,4-pentadienoylamino)benzolactam (TPPB), a structurally distinct PKC modulator, has a similar effect to bryo-1 on CNS innate immune cells both in vitro and in vivo, attenuating neuroinflammation and resulting in CNS regeneration and repair. This study identifies a new structural class of PKC modulators, which can therapeutically target CNS innate immunity as a strategy to treat neuroinflammatory and neurodegenerative disorders.

Indexed as

innate immunitymultiple sclerosisneurodegenerationneuroinflammationPKC modulatorremyelination

Identifiers

PMID38370818
PMCPMC10871289
OpenAlexW4391618445

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.