{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:18:08Z","timestamp":1787735888028,"version":"build-2784847793"},"reference-count":75,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Heart, Lung, and Blood Institute of the National Institutes of Health","award":["K01HL153210"],"award-info":[{"award-number":["K01HL153210"]}]},{"DOI":"10.13039\/100000050","name":"Programs to Increase Diversity Among Individuals Engaged in Health-Related Research Functional and Translational Genomics of Blood Disorders Program","doi-asserted-by":"publisher","award":["R25HL106365"],"award-info":[{"award-number":["R25HL106365"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Sickle 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. Methods: We performed high-resolution mass spectrometry on ultra-purified platelets from 16 adults with SCD and moderate to severe pain (self-reported \u2265 3\/10 in the past year), identifying 4196 proteins, of which 1046 were significant (FDR &lt; 0.05). Unsupervised clustering was used to stratify individuals into high- and low-pain phenotypes. Results: Contrary 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. Conclusions: These 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.<\/jats:p>","DOI":"10.3390\/medsci14050517","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:11:15Z","timestamp":1787731875000},"page":"517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Pain: A Pilot Study of Neurodegenerative and Mitochondrial Pathway Alterations in Sickle Cell Disease Using Platelet Proteomics"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8117-3445","authenticated-orcid":false,"given":"Keesha","family":"Powell-Roach","sequence":"first","affiliation":[{"name":"Rutgers Biomedical and Health Sciences, Division of Nursing Science, School of Nursing, Rutgers University, Newark, NJ 07107, USA"},{"name":"Department of Health Promotion and Disease Prevention, College of Nursing, University of Tennessee Health Science Center, Memphis, TN 38103, USA"},{"name":"Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-1414","authenticated-orcid":false,"given":"Ugochi O.","family":"Ogu","sequence":"additional","affiliation":[{"name":"Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Division of Hematology, University of Tennessee Health Science Center, Memphis, TN 38104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erielle","family":"Culp","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Disease Prevention, College of Nursing, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpna","family":"Gupta","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, University of California\u2014Irvine, Irvine, CA 92617, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7332-8777","authenticated-orcid":false,"given":"Eboni I.","family":"Lance","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA"},{"name":"Department of Neurodevelopmental Medicine, Kennedy Krieger Institute, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4396-7460","authenticated-orcid":false,"given":"Xueyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Health Promotion and Disease Prevention, College of Nursing, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2703-4011","authenticated-orcid":false,"given":"M. Dennis","family":"Leo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1600-6768","authenticated-orcid":false,"given":"Daniel","family":"Johnson","sequence":"additional","affiliation":[{"name":"Office of Research, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kakhniashvili","sequence":"additional","affiliation":[{"name":"Office of Research, University of Tennessee Health Science Center, Memphis, TN 38103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yenisel","family":"Cruz-Almeida","sequence":"additional","affiliation":[{"name":"Community Dentistry, College of Dentistry, University of Florida, Gainesville, FL 32606, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret R.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3954-8933","authenticated-orcid":false,"given":"Diana J.","family":"Wilkie","sequence":"additional","affiliation":[{"name":"Biobehavioral Nursing Science, College of Nursing, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7607-6525","authenticated-orcid":false,"given":"Steven R.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/oxfordjournals.aje.a010288","article-title":"Sickle hemoglobin (HbS) allele and sickle cell disease: A HuGE review","volume":"151","author":"Yang","year":"2000","journal-title":"Am. J. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1001\/jama.2010.610","article-title":"Neurocognitive complications of sickle cell anemia in adults","volume":"303","author":"Ballas","year":"2010","journal-title":"Jama"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102327","DOI":"10.1016\/j.ctim.2020.102327","article-title":"Review\/overview of pain in sickle cell disease","volume":"49","author":"Ballas","year":"2020","journal-title":"Complement. Ther. Med."},{"key":"ref_4","first-page":"305","article-title":"Sickle Cell Disease","volume":"377","author":"Piel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18010","DOI":"10.1038\/nrdp.2018.10","article-title":"Sickle cell disease","volume":"4","author":"Kato","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1182\/asheducation-2001.1.31","article-title":"Sickle Cell and the Brain","volume":"2001","author":"Adams","year":"2001","journal-title":"Hematology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1182\/blood.V97.6.1584","article-title":"Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress\u2013mediated vasodilation","volume":"97","author":"Belhassen","year":"2001","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s13105-022-00912-6","article-title":"Hypoxia: Molecular pathophysiological mechanisms in human diseases","volume":"78","author":"Fonticoli","year":"2022","journal-title":"J. Physiol. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/s41580-022-00456-z","article-title":"Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology","volume":"23","author":"Sies","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"B\u0142aszczyk, J.W. (2020). Energy Metabolism Decline in the Aging Brain-Pathogenesis of Neurodegenerative Disorders. Metabolites, 10.","DOI":"10.20944\/preprints202009.0539.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1182\/blood-2011-02-272682","article-title":"Silent cerebral infarcts: A review on a prevalent and progressive cause of neurologic injury in sickle cell anemia","volume":"119","author":"DeBaun","year":"2012","journal-title":"Blood"},{"key":"ref_12","unstructured":"Goodman, S.R. (2020). Goodman\u2019s Medical Cell Biology, Academic Press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1177\/09727531221108871","article-title":"Neurocognitive Changes in Sickle Cell Disease: A Comprehensive Review","volume":"29","author":"Sahu","year":"2022","journal-title":"Ann. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1016\/j.tips.2016.06.007","article-title":"Targeting Oxidative Stress in Central Nervous System Disorders","volume":"37","author":"Patel","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1182\/asheducation-2010.1.403","article-title":"Neurobiological mechanisms of pain in sickle cell disease","volume":"2010","author":"Wang","year":"2010","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/2049463720920682","article-title":"Mechanisms of pain in sickle cell disease","volume":"15","author":"Takaoka","year":"2021","journal-title":"Br. J. Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/MOH.0000000000000491","article-title":"Pain and sickle cell disease","volume":"26","author":"Aich","year":"2019","journal-title":"Curr. Opin. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1001\/jama.2010.562","article-title":"Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia","volume":"303","author":"Vichinsky","year":"2010","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104603","DOI":"10.1016\/j.jpain.2024.104603","article-title":"Unmet Need: Mechanistic and Translational Studies of Sickle Cell Disease Pain as a Whole-Person Health Challenge","volume":"25","author":"Belfer","year":"2024","journal-title":"J. Pain Off. J. Am. Pain Soc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1172\/JCI89741","article-title":"Intravascular hemolysis and the pathophysiology of sickle cell disease","volume":"127","author":"Kato","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.3324\/haematol.2019.239343","article-title":"Thromboinflammatory mechanisms in sickle cell disease\u2014Challenging the hemostatic balance","volume":"105","author":"Conran","year":"2020","journal-title":"Haematologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R104","DOI":"10.1152\/ajpregu.00021.2018","article-title":"Targeting pain at its source in sickle cell disease","volume":"315","author":"Gupta","year":"2018","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/s41586-025-08584-0","article-title":"Mass-spectrometry-based proteomics: From single cells to clinical applications","volume":"638","author":"Guo","year":"2025","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1182\/blood.2022015970","article-title":"The multifaceted role of platelets in mediating brain function","volume":"140","author":"Burnouf","year":"2022","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rawish, E., Nording, H., M\u00fcnte, T., and Langer, H.F. (2020). Platelets as Mediators of Neuroinflammation and Thrombosis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.548631"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2200013","DOI":"10.1002\/pmic.202200013","article-title":"Mass spectrometry-based high-throughput proteomics and its role in biomedical studies and systems biology","volume":"23","author":"Messner","year":"2023","journal-title":"Proteomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.4331\/wjbc.v12.i5.57","article-title":"Proteomics: Concepts and applications in human medicine","volume":"12","author":"Alshekaili","year":"2021","journal-title":"World J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the regulation of protein abundance from proteomic and transcriptomic analyses","volume":"13","author":"Vogel","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s00221-008-1419-4","article-title":"Proteomic analysis of differential proteins related to the neuropathic pain and neuroprotection in the dorsal root ganglion following its chronic compression in rats","volume":"189","author":"Zhang","year":"2008","journal-title":"Exp. Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pankratz, S., Bittner, S., Kehrel, B.E., Langer, H.F., Kleinschnitz, C., Meuth, S.G., and G\u00f6bel, K. (2016). The Inflammatory Role of Platelets: Translational Insights from Experimental Studies of Autoimmune Disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101723"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Leiter, O., and Walker, T.L. (2020). Platelets in Neurodegenerative Conditions-Friend or Foe?. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00747"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17448069251359601","DOI":"10.1177\/17448069251359601","article-title":"Mitochondrial dysfunction\/hyperfunction inducing excessive mtROS in inflammatory and neuropathic pain","volume":"21","author":"Zhu","year":"2025","journal-title":"Mol. Pain"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nesci, S. (2026). Mitochondrial Dysfunction in the Inflammatory Process of Neurodegenerative Diseases. Biomedicines, 14.","DOI":"10.3390\/biomedicines14030682"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kim, M.E., Lim, Y., and Lee, J.S. (2025). Mitochondrial Dysfunction and Metabolic Reprogramming in Chronic Inflammatory Diseases: Molecular Insights and Therapeutic Opportunities. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47121042"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101265","DOI":"10.1016\/j.xcrm.2023.101265","article-title":"Inflammation-induced mitochondrial and metabolic disturbances in sensory neurons control the switch from acute to chronic pain","volume":"4","author":"Willemen","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, H.M. (2025). Mitochondrial Dysfunction in Neurodegenerative Diseases. Cells, 14.","DOI":"10.3390\/cells14040276"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0885-3924(02)00638-3","article-title":"Usability of a computerized PAINReportIt in the general public with pain and people with cancer pain","volume":"25","author":"Wilkie","year":"2003","journal-title":"J. Pain Symptom Manag."},{"key":"ref_39","first-page":"18","article-title":"Patient-reported outcomes: Descriptors of nociceptive and neuropathic pain and barriers to effective pain management in adult outpatients with sickle cell disease","volume":"102","author":"Wilkie","year":"2010","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1089\/wound.2020.1355","article-title":"Multidimensional Pain Characteristics in Older Adults with Chronic Venous Leg Ulcers","volume":"10","author":"Kim","year":"2021","journal-title":"Adv. Wound Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/0742-969X.1990.11882662","article-title":"Cancer pain intensity measurement: Concurrent validity of three tools\u2014Finger dynamometer, pain intensity number scale, visual analogue scale","volume":"6","author":"Wilkie","year":"1990","journal-title":"Hosp. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jpain.2004.11.007","article-title":"The S-LANSS score for identifying pain of predominantly neuropathic origin: Validation for use in clinical and postal research","volume":"6","author":"Bennett","year":"2005","journal-title":"J. Pain Off. J. Am. Pain Soc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0304-3959(00)00482-6","article-title":"The LANSS Pain Scale: The Leeds assessment of neuropathic symptoms and signs","volume":"92","author":"Bennett","year":"2001","journal-title":"Pain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/NCC.0b013e3181faab63","article-title":"Differences in pain location, intensity, and quality by pain pattern in outpatients with cancer","volume":"34","author":"Ngamkham","year":"2011","journal-title":"Cancer Nurs."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.jpain.2005.11.008","article-title":"The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey","volume":"7","author":"Torrance","year":"2006","journal-title":"J. Pain Off. J. Am. Pain Soc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/0193945919836446","article-title":"Neuropathic Pain Screening: Construct Validity in Patients with Sickle Cell Disease","volume":"42","author":"Yao","year":"2020","journal-title":"West. J. Nurs. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0304-3959(75)90044-5","article-title":"The McGill Pain Questionnaire: Major properties and scoring methods","volume":"1","author":"Melzack","year":"1975","journal-title":"Pain"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Trichler, S.A., Bulla, S.C., Thomason, J., Lunsford, K.V., and Bulla, C. (2013). Ultra-pure platelet isolation from canine whole blood. BMC Vet. Res., 9.","DOI":"10.1186\/1746-6148-9-144"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/09537104.2016.1209478","article-title":"An efficient method for isolation of representative and contamination-free population of blood platelets for proteomic studies","volume":"28","author":"Wrzyszcz","year":"2017","journal-title":"Platelets"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/10409238.2023.2224532","article-title":"Platelet protein synthesis, regulation, and post-translational modifications: Mechanics and function","volume":"58","author":"Soslau","year":"2023","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/978-1-4939-7057-5_13","article-title":"Red Blood Cells in Clinical Proteomics","volume":"1619","author":"Carvalho","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1161\/CIRCRESAHA.113.300512","article-title":"Platelets as cellular effectors of inflammation in vascular diseases","volume":"112","author":"Rondina","year":"2013","journal-title":"Circ. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1042\/BST20253053","article-title":"UBQLN2 in neurodegenerative disease: Mechanistic insights and emerging therapeutic potential","volume":"53","author":"Matthews","year":"2025","journal-title":"Biochem. Soc. Trans."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Schmidt, A.F., Finan, C., Chopade, S., Ellmerich, S., Rossor, M.N., Hingorani, A.D., and Pepys, M.B. (2023). Genetic evidence for serum amyloid P component as a drug target for treatment of neurodegenerative disorders. medRxiv.","DOI":"10.1101\/2023.08.15.23293564"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1182\/blood-2013-09-529420","article-title":"Platelet bioenergetic screen in sickle cell patients reveals mitochondrial complex V inhibition, which contributes to platelet activation","volume":"123","author":"Cardenes","year":"2014","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1161\/ATVBAHA.120.314647","article-title":"Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease","volume":"41","author":"Aslan","year":"2021","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41419-021-04469-y","article-title":"BNIP3L\/NIX-mediated mitophagy: Molecular mechanisms and implications for human disease","volume":"13","author":"Li","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"301","DOI":"10.4161\/auto.7.3.14509","article-title":"Autophagy receptors in developmental clearance of mitochondria","volume":"7","author":"Novak","year":"2011","journal-title":"Autophagy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1586\/epr.10.88","article-title":"The proteome of sickle cell disease: Insights from exploratory proteomic profiling","volume":"7","author":"Yuditskaya","year":"2010","journal-title":"Expert. Rev. Proteom."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Alramadhani, D., Aljahdali, A.S., Abdulmalik, O., Pierce, B.D., and Safo, M.K. (2022). Metabolic Reprogramming in Sickle Cell Diseases: Pathophysiology and Drug Discovery Opportunities. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137448"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/MOH.0000000000000772","article-title":"Platelet mitochondria: The mighty few","volume":"30","author":"Ajanel","year":"2023","journal-title":"Curr. Opin. Hematol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1182\/bloodadvances.2019032334","article-title":"Nix-mediated mitophagy regulates platelet activation and life span","volume":"3","author":"Zhang","year":"2019","journal-title":"Blood Adv."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e1054","DOI":"10.1038\/cddis.2014.11","article-title":"Early and sustained altered expression of aging-related genes in young 3xTg-AD mice","volume":"5","author":"Gatta","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/ncb2012","article-title":"PINK1\/Parkin-mediated mitophagy is dependent on VDAC1 and p62\/SQSTM1","volume":"12","author":"Geisler","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1182\/blood.2020009063","article-title":"Circulating mitochondrial DNA is a proinflammatory DAMP in sickle cell disease","volume":"137","author":"Tumburu","year":"2021","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Akhter, M.S., Hamali, H.A., Rashid, H., Dobie, G., Madkhali, A.M., Mobarki, A.A., Oldenburg, J., and Biswas, A. (2023). Mitochondria: Emerging Consequential in Sickle Cell Disease. J. Clin. Med., 12.","DOI":"10.3390\/jcm12030765"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.exphem.2017.02.003","article-title":"Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease","volume":"50","author":"Jagadeeswaran","year":"2017","journal-title":"Exp. Hematol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.1111\/febs.16129","article-title":"UBQLN proteins in health and disease with a focus on UBQLN2 in ALS\/FTD","volume":"289","author":"Lin","year":"2022","journal-title":"Febs J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1111\/bjh.17416","article-title":"Deficient mitophagy pathways in sickle cell disease","volume":"193","author":"Martino","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3790","DOI":"10.1182\/bloodadvances.2024015085","article-title":"Molecular inflammatory expression profiles associated with the frequency of pain in individuals with sickle cell disease","volume":"9","author":"Jia","year":"2025","journal-title":"Blood Adv."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.1182\/blood.2020006020","article-title":"Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS) by patient-reported outcomes, actigraphy, and biomarkers","volume":"137","author":"Pittman","year":"2021","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Silva Santos Ribeiro, P., Willemen, H.L.D.M., and Eijkelkamp, N. (2022). Mitochondria and sensory processing in inflammatory and neuropathic pain. Front. 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