Evidence map›Paper›PMID 42783390›Full record

ArticleMedical sciences (Basel, Switzerland)2026

Beyond Pain: A Pilot Study of Neurodegenerative and Mitochondrial Pathway Alterations in Sickle Cell Disease Using Platelet Proteomics.

Keesha Powell-Roach, Ugochi O Ogu, Erielle Culp, Kalpna Gupta, Eboni I Lance, Xueyuan Cao, M Dennis Leo, Daniel Johnson, David Kakhniashvili, Yenisel Cruz-Almeida and 3 more

Abstract read
In one paragraph

Article in Medical sciences (Basel, Switzerland), 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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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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.

No citing paper in PubMed yet.

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.

Keesha Powell-RoachRutgers Biomedical and Health Sciences, Division of Nursing Science, School of Nursing, Rutgers University, Newark, NJ 07107, USA.ORCID 0000-0001-8117-3445
Ugochi O OguCenter for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA.ORCID 0000-0002-4662-1414
Erielle CulpDepartment of Health Promotion and Disease Prevention, College of Nursing, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Kalpna GuptaSchool of Pharmacy and Pharmaceutical Sciences, University of California-Irvine, Irvine, CA 92617, USA.
Eboni I LanceDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.ORCID 0000-0001-7332-8777
Xueyuan CaoDepartment of Health Promotion and Disease Prevention, College of Nursing, University of Tennessee Health Science Center, Memphis, TN 38103, USA.ORCID 0000-0002-4396-7460
M Dennis LeoDepartment of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.ORCID 0000-0002-2703-4011
Daniel JohnsonOffice of Research, University of Tennessee Health Science Center, Memphis, TN 38103, USA.ORCID 0000-0003-1600-6768
David KakhniashviliOffice of Research, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Yenisel Cruz-AlmeidaCommunity Dentistry, College of Dentistry, University of Florida, Gainesville, FL 32606, USA.
Margaret R WallaceDepartment of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Diana J WilkieBiobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL 32611, USA.ORCID 0000-0002-3954-8933
Steven R GoodmanCenter for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA.ORCID 0000-0002-7607-6525

Funding

PRIDE: Functional and Translational Genomics of Blood DisordersR25HL106365 · NHLBI · AUGUSTA UNIVERSITY · PI PACE, BETTY SUE · 2010 to 2024
$5.2M
Contributions of biopsychosocial factors in sickle cell disease painK01HL153210 · NHLBI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI ROACH, KEESHA L. · 2020 to 2023
$537k
National Heart Lung and Blood Institute R25HL106365NHLBI NIH HHS K01 HL153210NHLBI NIH HHS R25 HL106365
6 · The paper itself

Abstract

backgroundSickle cell disease (SCD) is a systemic disorder marked by chronic pain and neurocognitive deficits, yet the molecular drivers of these neurocognitive features remain poorly defined. Platelets, central to inflammation and vascular homeostasis, may reflect broad pathophysiologic processes in SCD.

methodsWe performed high-resolution mass spectrometry on ultra-purified platelets from 16 adults with SCD and moderate to severe pain (self-reported ≥ 3/10 in the past year), identifying 4196 proteins, of which 1046 were significant (FDR < 0.05). Unsupervised clustering was used to stratify individuals into high- and low-pain phenotypes.

resultsContrary to expectations, canonical pain pathways were not enriched. Instead, significant alterations were observed in neurodegeneration, mitochondrial metabolism, ATP regulation, mitophagy, and tRNA aminoacylation pathways between high- and low-pain phenotypes. High-pain individuals exhibited elevated levels of proteins involved in proteostasis and neurodegenerative disease processes, whereas low-pain individuals showed increased expression of proteins linked to mitochondrial integrity, neuroprotection, and reduced oxidative stress. Protein-protein interaction networks revealed tightly connected clusters within neurodegenerative and central nervous system-related pathways. Disease association analysis ranked neurodegenerative and mitochondrial pathways above traditional hematologic and nociceptive mechanisms.

conclusionsThese findings suggest that platelet proteomics may serve as a peripheral window into PNS or CNS vulnerability and cognitive risk in SCD. The enrichment of tRNA aminoacylation and mitochondrial regulation pathways underscores the metabolic complexity of SCD and highlights novel targets for biomarker development and therapeutic intervention.

Indexed as

Anemia, Sickle CellBlood PlateletsMitochondriaNeurodegenerative DiseasesPainProteomicsAdultFemaleHumansMalePilot ProjectsProteomeProteomemitochondrial dysfunctionneurodegeneration pathwaysoxidative stresspain phenotypesplatelet proteomicssickle cell disease

Identifiers

PMID42783390
PMCPMC13609081

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.