Evidence map›Paper›PMID 42115163›Full record

ArticleNature communications2026

α/Sulfonyl-γ-AApeptide foldamers mitigate Alzheimer's disease pathology by stabilizing transient helical domains in Aβ.

Heng Liu, Firoz Akhter, Asma Akhter, Xue Zhao, Xudong Wang, Haiqiang Yang, Jianyu Chen, Xinyu Xia, Laurent Calcul, Yi He and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

14 authors.

Heng Liu *Department of Chemistry, University of South Florida, Tampa, FL, USA.
Firoz Akhter *Department of Biomedical Engineering, University of Stony Brook, Stony Brook, NY, USA.ORCID http://orcid.org/0000-0002-8836-601X
Asma Akhter *Department of Biomedical Engineering, University of Stony Brook, Stony Brook, NY, USA.
Xue ZhaoDepartment of Chemistry, University of South Florida, Tampa, FL, USA.
Xudong WangDepartment of Molecular Biosciences, University of South Florida, Tampa, FL, USA.ORCID http://orcid.org/0000-0002-9686-2072
Haiqiang YangDepartment of Chemistry, University of South Florida, Tampa, FL, USA.
Jianyu ChenDepartment of Chemistry, University of South Florida, Tampa, FL, USA.
Xinyu XiaDepartment of Chemistry and Chemical Biology, The University of New Mexico, Albuquerque, NM, USA.
Laurent CalculDepartment of Chemistry, University of South Florida, Tampa, FL, USA.
Yi HeDepartment of Chemistry and Chemical Biology, The University of New Mexico, Albuquerque, NM, USA.
Chuanhai CaoTaneja College of Pharmacy, University of South Florida, Tampa, FL, USA.
Libin YeDepartment of Molecular Biosciences, University of South Florida, Tampa, FL, USA.ORCID http://orcid.org/0000-0003-0818-2972
Donghui ZhuDepartment of Biomedical Engineering, University of Stony Brook, Stony Brook, NY, USA. donghui.zhu@stonybrook.edu.ORCID http://orcid.org/0000-0002-3057-1889
Jianfeng CaiDepartment of Chemistry, University of South Florida, Tampa, FL, USA. jianfengcai@usf.edu.ORCID http://orcid.org/0000-0003-3106-3306

Funding

Recognition of Abeta monomeric helixR01AG056569 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI CHUANHAI CAO, Jianfeng Cai · 2017 to 2026
$4.1M
Inhibition of Abeta42 aggregation by helix stabilizing peptidomimetic biomaterialsRF1AG094856 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI CAI, JIANFENG, ZHU, DONGHUI · 2025 to 2025
$3.3M
Targeting Wnt signaling pathwayR01GM150196 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI Jianfeng Cai · 2023 to 2026
$1.7M
The Role of Intermediate Conformations in G Protein-coupled Receptor SignalingR01GM149659 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI Libin Ye · 2023 to 2026
$1.4M
NIA NIH HHS R01 AG056569NIA NIH HHS RF1 AG094856NIGMS NIH HHS R01 GM149659NIGMS NIH HHS R01 GM150196U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM150196U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG056569U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) RF1AG094856
6 · The paper itself

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ), with soluble oligomers widely recognized as key drivers of neurotoxicity through disruption of synaptic function, mitochondrial integrity, and cellular homeostasis. Targeting Aβ aggregation therefore represents a compelling therapeutic strategy. Here we report a synthetic peptidomimetic foldamer, M4, as a potent modulator of Aβ42 aggregation. Biophysical analyses demonstrate that M4 binds Aβ with high affinity, inhibits oligomer formation, and remodels pre-existing aggregates, likely by stabilizing a helical conformation that disfavors β-sheet assembly. In primary neurons, M4 restores synaptic protein levels, reduces oxidative stress, and preserves mitochondrial membrane potential. In a 5xFAD mouse model, M4 attenuates neuroinflammation, reduces Aβ burden, and improves cognitive performance. Pharmacokinetic studies further reveal favorable brain penetration and metabolic stability. Collectively, these findings establish M4 as a promising candidate for targeting Aβ-mediated pathology in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesPeptide FragmentsPeptidomimeticsAnimalsBrainDisease Models, AnimalHumansMembrane Potential, MitochondrialMiceMice, TransgenicNeuronsOxidative StressProtein Aggregation, PathologicalAmyloid beta-Peptidesamyloid beta-protein (1-42)Peptide FragmentsPeptidomimetics

Identifiers

PMID42115163
PMCPMC13377154

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.