A Small-Molecule TrkB Agonist Promotes Synaptic Resilience Against Aβ and Tau Oligomers and Mitigates Alterations in TrkB-Akt and Fyn Signaling.

Tao Yang, Kevin C Tran, Albert Leng, Vanessa F Langness, Stephen M Massa, Frank M Longo

Abstract read

In one paragraph

Article in Cells, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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.

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5 · Who and what money

Authors and funding

6 authors.

Tao YangDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-7698-3440

Kevin C TranDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.

Albert LengDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.

Vanessa F LangnessDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-3140-3008

Stephen M MassaDepartment of Neurology, San Francisco Veterans Affairs Health Care System, San Francisco, CA 94121, USA.ORCID 0000-0003-0474-4886

Frank M LongoDepartment of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0002-9514-7325

Funding

Horngren FamilyJean Perkins FoundationScully InitiativeTaube Family Foundation

6 · The paper itself

Abstract

backgroundPathogenic amyloid-beta and tau oligomers (oAβ, oTau) drive synaptic degeneration and cognitive decline in Alzheimer's disease (AD). Tropomyosin receptor kinase B (TrkB), expressed in neurons and glia, supports synaptic integrity in AD-affected regions. We tested whether PTX-BD4-3, a small-molecule TrkB partial agonist, promotes neuroprotective signaling, reduces degenerative signaling, and prevents synaptic loss in an AD mouse model and hippocampal neurons exposed to oAβ or oTau.

methodsCultured hippocampal neurons were treated with oAβ or oTau ± PTX-BD4-3. Effects on synaptic proteins (±TrkB-blocking antibody), spine density, and Fyn, NR2B, and tau phosphorylation as well as tau oligomerization were assessed. Two cohorts of APP

resultsIn vitro, PTX-BD4-3 prevented oAβ-induced synaptic marker loss in a TrkB-dependent manner, reduced phosphorylation of Fyn, NR2B, and tau, suppressed oligomeric tau formation, and attenuated oTau-induced spine loss. In APP

conclusionsSmall-molecule TrkB partial agonists may normalize TrkB signaling and promote synaptic resilience, supporting their potential as AD therapeutics.

Indexed as

Amyloid beta-PeptidesMembrane GlycoproteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-fynReceptor, trkBSynapsestau ProteinsAlzheimer DiseaseAnimalsDendritic SpinesHippocampusMaleMiceNeuronsPhosphorylationSignal TransductionAmyloid beta-PeptidesFyn protein, mouseMembrane GlycoproteinsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-fynReceptor, trkBtau ProteinsAktamyloid-betadendritic spineFynPTX-BD4-3resiliencesynapsetautropomyosin-receptor kinase B (TrkB)

Identifiers

PMID42882520

DOI10.3390/cells15191822

PMCPMC13664222

What OpenQuestion holds

Textmetadata

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.