Evidence map›Paper›PMID 37243896›Full record

ReviewProtein science : a publication of the Protein Society2023

Big versus small: The impact of aggregate size in disease.

Brianna Hnath, Jiaxing Chen, Joshua Reynolds, Esther Choi, Jian Wang, Dongyan Zhang, Congzhou M Sha, Nikolay V Dokholyan

Open access · bronzeAbstract readReview
In one paragraph

Review in Protein science : a publication of the Protein Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
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  3. Review
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  7. Big versus small: The impact of aggregate size in disease.Protein science : a publication of the Protein Society · 2023
    Review
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

8 authors at 2 institutions in 1 country.

Brianna HnathDepartment of Biomedical Engineering, Penn State University, University Park, Pennsylvania, USA.ORCID 0000-0003-0342-4522
Jiaxing ChenDepartment of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.ORCID 0000-0003-0150-1387
Joshua ReynoldsDepartment of Biomedical Engineering, Penn State University, University Park, Pennsylvania, USA.ORCID 0000-0001-6680-5993
Esther ChoiDepartment of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.ORCID 0000-0001-7494-300X
Jian WangDepartment of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.ORCID 0000-0001-7768-2802
Dongyan ZhangDepartment of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.ORCID 0000-0002-4513-3283
Congzhou M ShaDepartment of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.ORCID 0000-0001-5301-9459
Nikolay V DokholyanDepartment of Biomedical Engineering, Penn State University, University Park, Pennsylvania, USA.ORCID 0000-0002-8225-4025
Pennsylvania State University · USPenn State Milton S. Hershey Medical Center · US

Funding

Nanoscale programming of cellular and physiological phenotypes: EquipmentR35GM134864 · NIGMS · UNIVERSITY OF VIRGINIA · PI Nikolay Dokholyan · 2020 to 2026
$5.2M
AI-based Mapping of Complex Cannabis Extracts in Pain PathwaysR01AT012053 · NCCIH · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI Nikolay Dokholyan, KENT E VRANA · 2023 to 2026
$2.4M
Discovery of functionally selective dopamine ligands for age-related cognitive declineRF1AG071675 · NIA · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI DOKHOLYAN, NIKOLAY, MAILMAN, RICHARD B · 2021 to 2021
$1.5M
NCCIH NIH HHS R01 AT012053NIA NIH HHS RF1 AG071675NIGMS NIH HHS R35 GM134864
6 · The paper itself

Abstract

Protein aggregation results in an array of different size soluble oligomers and larger insoluble fibrils. Insoluble fibrils were originally thought to cause neuronal cell deaths in neurodegenerative diseases due to their prevalence in tissue samples and disease models. Despite recent studies demonstrating the toxicity associated with soluble oligomers, many therapeutic strategies still focus on fibrils or consider all types of aggregates as one group. Oligomers and fibrils require different modeling and therapeutic strategies, targeting the toxic species is crucial for successful study and therapeutic development. Here, we review the role of different-size aggregates in disease, and how factors contributing to aggregation (mutations, metals, post-translational modifications, and lipid interactions) may promote oligomers opposed to fibrils. We review two different computational modeling strategies (molecular dynamics and kinetic modeling) and how they are used to model both oligomers and fibrils. Finally, we outline the current therapeutic strategies targeting aggregating proteins and their strengths and weaknesses for targeting oligomers versus fibrils. Altogether, we aim to highlight the importance of distinguishing the difference between oligomers and fibrils and determining which species is toxic when modeling and creating therapeutics for protein aggregation in disease.

Indexed as

Neurodegenerative DiseasesProtein AggregatesAmyloidAmyloid beta-PeptidesHumansMolecular Dynamics SimulationAmyloidAmyloid beta-PeptidesProtein Aggregatesaggregationfibrilkinetic modelingmolecular dynamics simulationneurodegenerationoligomerpost-translational modification

Identifiers

PMID37243896
PMCPMC10273386
OpenAlexW4378529950

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.