{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:01:10Z","timestamp":1784253670653,"version":"3.55.0"},"reference-count":119,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease and Parkinson\u2019s disease remain the most prevalent neurodegenerative disorders associated with aging and continue to lack curative treatments. Their pathophysiology is often multifaceted, encompassing protein aggregation, mitochondrial dysfunction, chronic neuroinflammation, synaptic degeneration, and vascular compromise. This complex landscape reduces the effectiveness of single-target pharmacological agents and underscores the need for therapies capable of acting across multiple axes. Orthobiologics and peptide-based strategies exemplify this approach. Autologous cellular alternatives such as platelet-rich plasma, bone marrow aspirates, mesenchymal stromal cell derivatives, and extracellular vesicles deliver paracrine signals that can reprogram glia, preserve mitochondrial function, and promote synaptic and vascular repair. Peptide therapeutics, including glucagon-like peptide-1 receptor agonists and novel sequences targeting protein aggregation or mitochondrial pathways, provide complementary precision by engaging defined receptors and intracellular cascades. Together, these modalities converge on mechanisms central to circuit preservation rather than symptomatic relief alone. Preclinical studies across Alzheimer\u2019s and Parkinson\u2019s disease demonstrate consistent neuroprotective and functional benefits, and early human trials support feasibility and safety. The translational path forward requires standardized preparation, biomarker integration, optimized delivery routes such as intranasal administration, and regulatory frameworks adapted to biologic therapies. This review synthesizes current evidence on orthobiologics and peptides in neurodegeneration, outlines safety and translational considerations, and highlights future directions, including rational combinations and biomarker-driven trials. By uniting the broad signaling capacity of orthobiologics with the precision of peptides, neurology can move beyond symptomatic care toward regenerative strategies that aim to preserve neural circuits and improve long-term outcomes in Alzheimer\u2019s disease and Parkinson\u2019s disease.<\/jats:p>","DOI":"10.3390\/cells14231853","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T10:46:18Z","timestamp":1764067578000},"page":"1853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Orthobiologics and Peptide Therapy for Central Nervous System Repair in Neurodegenerative Conditions"],"prefix":"10.3390","volume":"14","author":[{"given":"C\u00e9zar Augusto Alves","family":"de Oliveira","sequence":"first","affiliation":[{"name":"Neurosurgery, Bioquest Clinic, S\u00e3o Paulo 04508-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo Scaldini","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Orthopedics, Regeneris Clinic, S\u00e3o Paulo 01404-001, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Scaldini","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Nutrology, Regeneris Clinic, S\u00e3o Paulo 01404-001, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Duarte","family":"de Souza Loduca","sequence":"additional","affiliation":[{"name":"Neurosurgery, Tratar Institute, S\u00e3o Paulo 05426-100, SP, Brazil"},{"name":"Neurosurgery, Military Area Hospital of S\u00e3o Paulo (HMASP), S\u00e3o Paulo 01551-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Roberto Massella","family":"Junior","sequence":"additional","affiliation":[{"name":"Neurosurgery, Tratar Institute, S\u00e3o Paulo 05426-100, SP, Brazil"},{"name":"Neurosurgery, Military Area Hospital of S\u00e3o Paulo (HMASP), S\u00e3o Paulo 01551-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0549-6821","authenticated-orcid":false,"given":"Gabriel Silva","family":"Santos","sequence":"additional","affiliation":[{"name":"Brazilian Institute of Regenerative Medicine (BIRM), Indaiatuba 13334-170, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sequeira, L., Benfeito, S., Fernandes, C., Lima, I., Peixoto, J., Alves, C., Machado, C.S., Gaspar, A., Borges, F., and Chavarria, D. (2024). Drug Development for Alzheimer\u2019s and Parkinson\u2019s Disease: Where Do We Go Now?. Pharmaceutics, 16.","DOI":"10.20944\/preprints202404.0437.v1"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104062","DOI":"10.1016\/j.drudis.2024.104062","article-title":"Selenium-containing compounds: A new hope for innovative treatments in Alzheimer\u2019s disease and Parkinson\u2019s disease","volume":"29","author":"Pyka","year":"2024","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41392-025-02145-7","article-title":"Antiageing strategy for neurodegenerative diseases: From mechanisms to clinical advances","volume":"10","author":"Jiang","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Monti, G., Moreira, D.G., Richner, M., Mutsaers, H.A.M., Ferreira, N., and Jan, A. (2022). GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight. Cells, 11.","DOI":"10.3390\/cells11132023"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Costa, F.R., Pires, L., Martins, R.A., Santos, M., Santos, G.S., Lana, J.V., Costa, B.R., Santos, N., de Macedo, A.P., and Kruel, A. (2025). Orthobiologics Revisited: A Concise Perspective on Regenerative Orthopedics. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47040247"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-023-05672-9","article-title":"Alpha-synuclein in Parkinson\u2019s disease and other synucleinopathies: From overt neurodegeneration back to early synaptic dysfunction","volume":"14","author":"Calabresi","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"975","DOI":"10.3233\/JAD-160612","article-title":"Amyloid Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer\u2019s disease Neurons","volume":"57","author":"Rajmohan","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e70107","DOI":"10.1111\/bcpt.70107","article-title":"Emerging Molecular Targets in Neurodegenerative Disorders: New Avenues for Therapeutic Intervention","volume":"137","author":"Eroglu","year":"2025","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lana, J.V., Rios, A., Takeyama, R., Santos, N., Pires, L., Santos, G.S., Rodrigues, I.J., Jeyaraman, M., Purita, J., and Lana, J.F. (2024). Nebulized Glutathione as a Key Antioxidant for the Treatment of Oxidative Stress in Neurodegenerative Conditions. Nutrients, 16.","DOI":"10.3390\/nu16152476"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Alkhalifa, A.E., Alkhalifa, O., Durdanovic, I., Ibrahim, D.R., and Maragkou, S. (2025). Oxidative Stress and Mitochondrial Dysfunction in Alzheimer\u2019s Disease: Insights into Pathophysiology and Treatment. J. Dement. Alzheimers Dis., 2.","DOI":"10.20944\/preprints202408.1375.v2"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mani, S., Wasnik, S., Shandilya, C., Srivastava, V., Khan, S., and Singh, K.K. (2025). Pathogenic synergy: Dysfunctional mitochondria and neuroinflammation in neurodegenerative diseases associated with aging. Front. Aging, 6.","DOI":"10.3389\/fragi.2025.1615764"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yang, X., Zhou, P., Zhao, Z., Li, J., Fan, Z., Li, X., Cui, Z., and Fu, A. (2023). Improvement Effect of Mitotherapy on the Cognitive Ability of Alzheimer\u2019s Disease through NAD+\/SIRT1-Mediated Autophagy. Antioxidants, 12.","DOI":"10.3390\/antiox12112006"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102077","DOI":"10.1016\/j.mito.2025.102077","article-title":"Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer\u2019s disease","volume":"85","author":"Gupta","year":"2025","journal-title":"Mitochondrion"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1096\/fj.201700600R","article-title":"Exosomes derived from hypoxia-preconditioned mesenchymal stromal cells ameliorate cognitive decline by rescuing synaptic dysfunction and regulating inflammatory responses in APP\/PS1 mice","volume":"32","author":"Cui","year":"2018","journal-title":"FASEB J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1007\/s11064-018-2641-5","article-title":"Exosomes Isolated From Human Umbilical Cord Mesenchymal Stem Cells Alleviate Neuroinflammation and Reduce Amyloid-Beta Deposition by Modulating Microglial Activation in Alzheimer\u2019s Disease","volume":"43","author":"Ding","year":"2018","journal-title":"Neurochem. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.14336\/AD.2021.0516","article-title":"Extracellular Vesicles for the Diagnosis and Treatment of Parkinson\u2019s Disease","volume":"12","author":"Upadhya","year":"2021","journal-title":"Aging Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Cueva, E., Wiesheu, A., Sordo, Z., Gonz\u00e1lez, J., Falconi, S., Rodas, J.A., and Leon-Rojas, J.E. (2025). Tissue Stem Cell-Based Therapies in Parkinson\u2019s Disease: A Scoping Review of Therapeutic Mechanisms and Translational Outcomes. Cells, 14.","DOI":"10.3390\/cells14110822"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41419-020-2473-5","article-title":"Exosomes derived from mesenchymal stem cells repair a Parkinson\u2019s disease model by inducing autophagy","volume":"11","author":"Chen","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","article-title":"The blood\u2013brain barrier: Structure, regulation and drug delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1016\/j.apsb.2022.04.001","article-title":"New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders: Combining with intranasal delivery","volume":"12","author":"Li","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1002\/stem.3456","article-title":"Intranasal Delivery of Mesenchymal Stem Cells-Derived Extracellular Vesicles for the Treatment of Neurological Diseases","volume":"39","author":"Herman","year":"2021","journal-title":"Stem Cells"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/sctm.18-0162","article-title":"Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats","volume":"8","author":"Narbute","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1208\/s12248-015-9719-7","article-title":"Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases","volume":"17","author":"Meredith","year":"2015","journal-title":"AAPS J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Turano, E., Scambi, I., Virla, F., Bonetti, B., and Mariotti, R. (2023). Extracellular Vesicles from Mesenchymal Stem Cells: Towards Novel Therapeutic Strategies for Neurodegenerative Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032917"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Williams, A., Branscome, H., Kashanchi, F., and Batrakova, E.V. (2025). Targeting of Extracellular Vesicle-Based Therapeutics to the Brain. Cells, 14.","DOI":"10.3390\/cells14070548"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/cpt.2531","article-title":"Translational Approaches for Brain Delivery of Biologics via Cerebrospinal Fluid","volume":"111","author":"Sadekar","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e13123","DOI":"10.1111\/cpr.13123","article-title":"Platelet-rich plasma-derived extracellular vesicles: A superior alternative in regenerative medicine?","volume":"54","author":"Wu","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"155560","DOI":"10.1016\/j.cyto.2021.155560","article-title":"The regenerative mechanisms of platelet-rich plasma: A review","volume":"144","author":"Santos","year":"2021","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Delila, L., Nebie, O., Le, N.T.N., Timmerman, K., Lee, D.-Y., Wu, Y.-W., Chou, M.-L., Bu\u00e9e, L., Chou, S.-Y., and Blum, D. (2024). Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson\u2019s disease models. J. Biomed. Sci., 31.","DOI":"10.1186\/s12929-024-01072-z"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1002\/mds.28582","article-title":"Allogeneic Bone Marrow\u2013Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson\u2019s Disease","volume":"36","author":"Schiess","year":"2021","journal-title":"Mov. Disord."},{"key":"ref_31","unstructured":"Schiess, M. (2024, September 10). A Randomized, Double-Blind, Placebo-Controlled Trial of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells as a Disease-Modifying Therapy for Idiopathic Parkinson\u2019s Disease. clinicaltrials.gov, Available online: https:\/\/clinicaltrials.gov\/study\/NCT04506073."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Precious, S.V., Smith, G.A., Heuer, A., Jaeger, I., Lane, E.L., Dunnett, S.B., Li, M., Kelly, C.M., and Rosser, A.E. (2020). Dopaminergic Progenitors Derived From Epiblast Stem Cells Function Similarly to Primary VM-Derived Progenitors When Transplanted Into a Parkinson\u2019s Disease Model. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00312"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00712","DOI":"10.1016\/j.neurot.2025.e00712","article-title":"From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics","volume":"22","author":"Roy","year":"2025","journal-title":"Neurotherapeutics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100645","DOI":"10.1016\/j.medj.2025.100645","article-title":"GLP-1 agonists to slow down Parkinson\u2019s progression? The quest continues","volume":"6","author":"Bloem","year":"2025","journal-title":"Med"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13195-022-00959-z","article-title":"A novel D-amino acid peptide with therapeutic potential (ISAD1) inhibits aggregation of neurotoxic disease-relevant mutant Tau and prevents Tau toxicity in vitro","volume":"14","author":"Aillaud","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7788","DOI":"10.1002\/alz.14246","article-title":"A novel peptide-based tau aggregation inhibitor as a potential therapeutic for Alzheimer\u2019s disease and other tauopathies","volume":"20","author":"Aggidis","year":"2024","journal-title":"Alzheimers Dement."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hu, D., Sun, X., and Qi, X. (2025). Targeting the ClpP-\u03b1Synuclein Interaction with a Decoy Peptide to Mitigate Neuropathology in Parkinson\u2019s Disease Models. bioRxiv.","DOI":"10.1101\/2025.02.16.638540"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Popova, B., Wang, D., Rajavel, A., Dhamotharan, K., L\u00e1zaro, D.F., Gerke, J., Uhrig, J.F., Hoppert, M., Outeiro, T.F., and Braus, G.H. (2021). Identification of Two Novel Peptides That Inhibit \u03b1-Synuclein Toxicity and Aggregation. Front. Mol. Neurosci., 14.","DOI":"10.3389\/fnmol.2021.659926"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nhu, N.T., Xiao, S.-Y., Liu, Y., Kumar, V.B., Cui, Z.-Y., and Lee, S.-D. (2022). Neuroprotective Effects of a Small Mitochondrially-Targeted Tetrapeptide Elamipretide in Neurodegeneration. Front. Integr. Neurosci., 15.","DOI":"10.3389\/fnint.2021.747901"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.bbrc.2023.02.076","article-title":"The mitochondria-targeted small molecule SS31 delays progression of behavioral deficits by attenuating \u03b2-amyloid plaque formation and mitochondrial\/synaptic deterioration in APP\/PS1 mice","volume":"658","author":"Jia","year":"2023","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12974-019-1627-9","article-title":"Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice","volume":"16","author":"Zhao","year":"2019","journal-title":"J. Neuroinflam."},{"key":"ref_42","first-page":"350","article-title":"Extracellular vesicles as carriers for protein and peptide therapeutics delivery: A review","volume":"3","author":"Mengesha","year":"2025","journal-title":"Intell. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.4103\/NRR.NRR-D-24-01591","article-title":"Dysregulated insulin signaling and inflammation contribute to the pathogenesis of Alzheimer\u2019s disease: From animal models to human cells","volume":"21","author":"Rytter","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"25424823251361056","DOI":"10.1177\/25424823251361056","article-title":"Insulin resistance and Alzheimer\u2019s disease: Exploring research hotspots and frontiers from a bibliometric and visual analysis (2005\u20132024)","volume":"9","author":"Zhang","year":"2025","journal-title":"J. Alzheimers Dis. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"745","DOI":"10.4239\/wjd.v12.i6.745","article-title":"Alzheimer\u2019s disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links","volume":"12","author":"Rojas","year":"2021","journal-title":"World J. Diabetes"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41392-024-02107-5","article-title":"Advance in peptide-based drug development: Delivery platforms, therapeutics and vaccines","volume":"10","author":"Xiao","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"18","DOI":"10.4103\/1673-5374.343882","article-title":"Extracellular vesicles in Alzheimer\u2019s disease: From pathology to therapeutic approaches","volume":"18","author":"Thakor","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_48","first-page":"S222","article-title":"Predicting progression of mild cognitive impairment patients through four distinctive subgroups obtained by unsupervised learning algorithms","volume":"108","author":"Baldeiras","year":"2025","journal-title":"J. Alzheimers Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e70790","DOI":"10.1002\/alz.70790","article-title":"Neurometabolic and vascular dysfunction as an early diagnostic for Alzheimer\u2019s disease and related dementias","volume":"21","author":"Persohn","year":"2025","journal-title":"Alzheimers Dement."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Aquilani, R., Cotta Ramusino, M., Maestri, R., Iadarola, P., Boselli, M., Perini, G., Boschi, F., Dossena, M., Bellini, A., and Buonocore, D. (2023). Several dementia subtypes and mild cognitive impairment share brain reduction of neurotransmitter precursor amino acids, impaired energy metabolism, and lipid hyperoxidation. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1237469"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Oporto-Colicoi, V., Sep\u00falveda-Lara, A., Marzuca-Nassr, G.N., and Sep\u00falveda-Figueroa, P. (2025). Mild Cognitive Impairment and Sarcopenia: Effects of Resistance Exercise Training on Neuroinflammation, Cognitive Performance, and Structural Brain Changes. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262211036"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Limanaqi, F., Biagioni, F., Gambardella, S., Familiari, P., Frati, A., and Fornai, F. (2020). Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21083028"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"104023","DOI":"10.1016\/j.mcn.2025.104023","article-title":"Rethinking Parkinson\u2019s: The role of proteostasis networks and autophagy in disease progression","volume":"134","author":"Sharma","year":"2025","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13024-023-00617-4","article-title":"Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer\u2019s disease","volume":"18","author":"Morrone","year":"2023","journal-title":"Mol. Neurodegener."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Misrani, A., Tabassum, S., and Yang, L. (2021). Mitochondrial Dysfunction and Oxidative Stress in Alzheimer\u2019s Disease. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.617588"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Blesa, J., Trigo-Damas, I., Quiroga-Varela, A., and Jackson-Lewis, V.R. (2015). Oxidative stress and Parkinson\u2019s disease. Front. Neuroanat., 9.","DOI":"10.3389\/fnana.2015.00091"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Steffan, D., Pezzini, C., Esposito, M., and Franco-Romero, A. (2025). Mitochondrial Aging in the CNS: Unravelling Implications for Neurological Health and Disease. Biomolecules, 15.","DOI":"10.3390\/biom15091252"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e2025847118","DOI":"10.1073\/pnas.2025847118","article-title":"Soluble \u03b1-synuclein\u2013antibody complexes activate the NLRP3 inflammasome in hiPSC-derived microglia","volume":"118","author":"Trudler","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13024-025-00870-9","article-title":"Glial phagocytosis for synapse and toxic proteins in neurodegenerative diseases","volume":"20","author":"Choi","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Batista, A.F., Khan, K.A., Papavergi, M.-T., and Lemere, C.A. (2024). The Importance of Complement-Mediated Immune Signaling in Alzheimer\u2019s Disease Pathogenesis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020817"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.immuni.2024.03.010","article-title":"Innate immune activation in neurodegenerative diseases","volume":"57","author":"Heneka","year":"2024","journal-title":"Immunity"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Kim, S., Jung, U.J., and Kim, S.R. (2024). Role of Oxidative Stress in Blood\u2013Brain Barrier Disruption and Neurodegenerative Diseases. Antioxidants, 13.","DOI":"10.3390\/antiox13121462"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Novoa, C., Salazar, P., Cisternas, P., Gherardelli, C., Vera-Salazar, R., Zolezzi, J.M., and Inestrosa, N.C. (2022). Inflammation context in Alzheimer\u2019s disease, a relationship intricate to define. Biol. Res., 55.","DOI":"10.1186\/s40659-022-00404-3"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in neurodegenerative diseases: Mechanism and potential therapeutic targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e0675242024","DOI":"10.1523\/JNEUROSCI.0675-24.2024","article-title":"Amyloid-\u03b2 Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling","volume":"44","author":"Prikhodko","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-981-32-9358-8_7","article-title":"Tau and Axonal Transport Misregulation in Tauopathies","volume":"1184","author":"Combs","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Brzozowski, C.F., Challa, H., Gcwensa, N.Z., Hall, D., Nabert, D., Chambers, N., Gallardo, I., Millet, M., Volpicelli-Daley, L., and Moehle, M.S. (2025). Early \u03b1-synuclein aggregation decreases corticostriatal glutamate drive and synapse density. Neurobiol. Dis., 210.","DOI":"10.1016\/j.nbd.2025.106918"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13024-018-0286-0","article-title":"Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-\u03b242 by LRP1-dependent apolipoprotein E isoform-specific mechanism","volume":"13","author":"Ma","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40035-024-00430-z","article-title":"Blood\u2013brain barrier alterations and their impact on Parkinson\u2019s disease pathogenesis and therapy","volume":"13","author":"Lau","year":"2024","journal-title":"Transl. Neurodegener."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Paul, G., and Elabi, O.F. (2022). Microvascular Changes in Parkinson\u2019s Disease- Focus on the Neurovascular Unit. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.853372"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Li, W., Fu, Y., Halliday, G.M., and Sue, C.M. (2021). PARK Genes Link Mitochondrial Dysfunction and Alpha-Synuclein Pathology in Sporadic Parkinson\u2019s Disease. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.612476"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41420-025-02600-y","article-title":"The multifaceted roles of apolipoprotein E4 in Alzheimer\u2019s disease pathology and potential therapeutic strategies","volume":"11","author":"Chen","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1093\/hmg\/ddad102","article-title":"Mitochondrial dysfunction and mitophagy defects in LRRK2-R1441C Parkinson\u2019s disease models","volume":"32","author":"Williamson","year":"2023","journal-title":"Hum. Mol. Genet."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Lossi, L., Castagna, C., and Merighi, A. (2024). An Overview of the Epigenetic Modifications in the Brain under Normal and Pathological Conditions. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073881"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Nam, G.E., Kim, S.M., Han, K., Kim, N.H., Chung, H.S., Kim, J.W., Han, B., Cho, S.J., Yu, J.H., and Park, Y.G. (2018). Metabolic syndrome and risk of Parkinson disease: A nationwide cohort study. PLoS Med., 15.","DOI":"10.1371\/journal.pmed.1002640"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Yoon, J.H., Hwang, J., Son, S.U., Choi, J., You, S.-W., Park, H., Cha, S.-Y., and Maeng, S. (2023). How Can Insulin Resistance Cause Alzheimer\u2019s Disease?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043506"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Pfaffinger, J.M., Hays, K.E., Seeley, J., Ramesh Babu, P., and Ryznar, R. (2025). Gut dysbiosis as a potential driver of Parkinson\u2019s and Alzheimer\u2019s disease pathogenesis. Front. Neurosci., 19.","DOI":"10.3389\/fnins.2025.1600148"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Hermann, D.M., Wang, C., Mohamud Yusuf, A., Herz, J., Doeppner, T.R., and Giebel, B. (2025). Extracellular vesicles lay the ground for neuronal plasticity by restoring mitochondrial function, cell metabolism and immune balance. J. Cereb. Blood Flow. Metab., ahead of print.","DOI":"10.1177\/0271678X251325039"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Regmi, S., Liu, D.D., Shen, M., Kevadiya, B.D., Ganguly, A., Primavera, R., Chetty, S., Yarani, R., and Thakor, A.S. (2022). Mesenchymal stromal cells for the treatment of Alzheimer\u2019s disease: Strategies and limitations. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1011225"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"102421","DOI":"10.4252\/wjsc.v17.i4.102421","article-title":"Effectiveness of mesenchymal stem cell-derived extracellular vesicles therapy for Parkinson\u2019s disease: A systematic review of preclinical studies","volume":"17","author":"Wang","year":"2025","journal-title":"World J. Stem Cells"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Lana, J.F., Purita, J., Jeyaraman, M., de Souza, B.F., Rodrigues, B.L., Huber, S.C., Caliari, C., Santos, G.S., da Fonseca, L.F., and Dallo, I. (2024). Innovative Approaches in Knee Osteoarthritis Treatment: A Comprehensive Review of Bone Marrow-Derived Products. Biomedicines, 12.","DOI":"10.3390\/biomedicines12122812"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e18120","DOI":"10.1016\/j.heliyon.2023.e18120","article-title":"Secretome-based acellular therapy of bone marrow-derived mesenchymal stem cells in degenerative and immunological disorders: A narrative review","volume":"9","author":"Zohora","year":"2023","journal-title":"Heliyon"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Lana, J.F., Navani, A., Jeyaraman, M., Santos, N., Pires, L., Santos, G.S., Rodrigues, I.J., Santos, D., Mosaner, T., and Azzini, G. (2024). Sacral Bioneuromodulation: The Role of Bone Marrow Aspirate in Spinal Cord Injuries. Bioengineering, 11.","DOI":"10.3390\/bioengineering11050461"},{"key":"ref_84","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_85","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1021\/acsbiomaterials.5c00473","article-title":"Platelet Extracellular Vesicles as Natural Delivery Vehicles for Mitochondrial Dysfunction Therapy?","volume":"11","author":"Yeh","year":"2025","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular vesicles as tools and targets in therapy for diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Spakova, T., Janockova, J., and Rosocha, J. (2021). Characterization and Therapeutic Use of Extracellular Vesicles Derived from Platelets. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189701"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"29","DOI":"10.13105\/wjma.v9.i1.29","article-title":"Biofat grafts as an orthobiologic tool in osteoarthritis: An update and classification proposal","volume":"9","author":"Macedo","year":"2021","journal-title":"World J. Meta-Anal."},{"key":"ref_89","first-page":"11","article-title":"Stromal Vascular Fraction for Knee Osteoarthritis\u2014An Update","volume":"18","author":"Lana","year":"2022","journal-title":"J. Stem Cells Regen. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Feng, H., Gong, S., Liu, J., Aghayants, S., Liu, Y., Wu, M., Wu, Y., and Song, J. (2025). Adipose-derived stem cell exosomes: Mechanisms and therapeutic potentials in wound healing. Biomark. Res., 13.","DOI":"10.1186\/s40364-025-00801-2"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Urkon, M., Ferencz, E., Sz\u00e1sz, J.A., Szabo, M.I.M., Orb\u00e1n-Kis, K., Szatm\u00e1ri, S., and Nagy, E.E. (2025). Antidiabetic GLP-1 Receptor Agonists Have Neuroprotective Properties in Experimental Animal Models of Alzheimer\u2019s Disease. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050614"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0140-6736(24)02808-3","article-title":"Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson\u2019s disease in the UK: A phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial","volume":"405","author":"Vijiaratnam","year":"2025","journal-title":"Lancet"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Liao, J., He, W., Li, L., Wang, J., Gong, L., Zhang, Q., and Lin, Z. (2025). Mitochondria in brain diseases: Bridging structural-mechanistic insights into precision-targeted therapies. Cell Biomater., 1.","DOI":"10.1016\/j.celbio.2025.100016"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lu, J., Cao, Q., Wang, C., Zheng, J., Luo, F., Xie, J., Li, Y., Ma, X., He, L., and Eisenberg, D. (2019). Structure-Based Peptide Inhibitor Design of Amyloid-\u03b2 Aggregation. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00054"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1021\/jacsau.5c00269","article-title":"Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies","volume":"5","author":"Murakami","year":"2025","journal-title":"JACS Au"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.chembiol.2020.12.010","article-title":"A SUMO1-Derived Peptide Targeting SUMO-Interacting Motif Inhibits \u03b1-Synuclein Aggregation","volume":"28","author":"Liang","year":"2021","journal-title":"Cell Chem. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ikeda, T., Kawabori, M., Zheng, Y., Yamaguchi, S., Gotoh, S., Nakahara, Y., Yoshie, E., and Fujimura, M. (2024). Intranasal Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Hypoxic-Ischemic Brain Injury. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16040446"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"113853","DOI":"10.1016\/j.intimp.2024.113853","article-title":"Intranasal delivery of mesenchymal stem cell-derived exosomes ameliorates experimental autoimmune encephalomyelitis","volume":"146","author":"Wu","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Li, P., Sun, S., Zhu, X., Liu, X., Yin, R., Chen, Y., Chang, J., Ye, L., Gao, J., and Zhao, X. (2025). Intranasal delivery of engineered extracellular vesicles promotes neurofunctional recovery in traumatic brain injury. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03181-9"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Schreiner, T.G., Men\u00e9ndez-Gonz\u00e1lez, M., Schreiner, O.D., and Ciobanu, R.C. (2025). Intrathecal Therapies for Neurodegenerative Diseases: A Review of Current Approaches and the Urgent Need for Advanced Delivery Systems. Biomedicines, 13.","DOI":"10.3390\/biomedicines13092167"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.addr.2021.03.002","article-title":"Harnessing cerebrospinal fluid circulation for drug delivery to brain tissues","volume":"173","author":"Feldsien","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Hassanpour, M., Rezabakhsh, A., Rezaie, J., Nouri, M., and Rahbarghazi, R. (2020). Exosomal cargos modulate autophagy in recipient cells via different signaling pathways. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00455-7"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"112781","DOI":"10.1016\/j.exger.2025.112781","article-title":"Mesenchymal stem cells and exosomes: A novel therapeutic approach for aging","volume":"206","author":"Lan","year":"2025","journal-title":"Exp. Gerontol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.tins.2025.09.008","article-title":"Mesenchymal stromal cell extracellular vesicles as immune modulators and drug carriers in neurodegenerative disorders","volume":"48","author":"Lucci","year":"2025","journal-title":"Trends Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Qin, Q., Fan, L., Zeng, X., Zheng, D., Wang, H., Li, M., Jiang, Y., Wang, H., Liu, H., and Liang, S. (2025). Mesenchymal stem cell-derived extracellular vesicles alleviate autism by regulating microglial glucose metabolism reprogramming and neuroinflammation through PD-1\/PD-L1 interaction. J. Nanobiotechnol., 23.","DOI":"10.1186\/s12951-025-03250-z"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1097\/TA.0000000000002230","article-title":"Regulation of endothelial cell permeability by platelet-derived extracellular vesicles","volume":"86","author":"Miyazawa","year":"2019","journal-title":"J. Trauma. Acute Care Surg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e13312","DOI":"10.1111\/cpr.13312","article-title":"Human platelet lysate-derived extracellular vesicles enhance angiogenesis through miR-126","volume":"55","author":"Bordin","year":"2022","journal-title":"Cell Prolif."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/s13287-024-04065-9","article-title":"Comparative analysis of regulations and studies on stem cell therapies: Focusing on induced pluripotent stem cell (iPSC)-based treatments","volume":"15","author":"Song","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"7","DOI":"10.21037\/sci-2022-025","article-title":"Adverse events, side effects and complications in mesenchymal stromal cell-based therapies","volume":"9","author":"Baranovskii","year":"2022","journal-title":"Stem Cell Investig."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3852898","DOI":"10.1155\/2022\/3852898","article-title":"Variability in Platelet-Rich Plasma Preparations Used in Regenerative Medicine: A Comparative Analysis","volume":"2022","author":"Tey","year":"2022","journal-title":"Stem Cells Int."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Jeyaraman, M., Bingi, S.K., Muthu, S., Jeyaraman, N., Packkyarathinam, R.P., Ranjan, R., Sharma, S., Jha, S.K., Khanna, M., and Rajendran, S.N.S. (2022). Impact of the Process Variables on the Yield of Mesenchymal Stromal Cells from Bone Marrow Aspirate Concentrate. Bioengineering, 9.","DOI":"10.3390\/bioengineering9020057"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Al Musaimi, O., Lombardi, L., Williams, D.R., and Albericio, F. (2022). Strategies for Improving Peptide Stability and Delivery. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101283"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.jacc.2025.08.027","article-title":"Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists","volume":"86","author":"Galli","year":"2025","journal-title":"JACC"},{"key":"ref_114","first-page":"212283","article-title":"A clinical review of GLP-1 receptor agonists: Efficacy and safety in diabetes and beyond","volume":"4","author":"Isaacs","year":"2015","journal-title":"Drugs Context"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1053\/j.trap.2016.09.004","article-title":"Bone marrow concentrate and platelet-rich plasma acquisition and preparation: Why technique matters","volume":"19","author":"Murphy","year":"2015","journal-title":"Tech. Reg. Anesth. Pain Manag."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1002\/jor.24786","article-title":"The platelet-rich plasma and mesenchymal stem cell milieu: A review of therapeutic effects on bone healing","volume":"38","author":"Liebig","year":"2020","journal-title":"J. Orthop. Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/hcs2.70028","article-title":"Exploring Regulatory Frameworks for Exosome Therapy: Insights and Perspectives","volume":"4","author":"Li","year":"2025","journal-title":"Health Care Sci."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Bell, S.M., Barnes, K., De Marco, M., Shaw, P.J., Ferraiuolo, L., Blackburn, D.J., Venneri, A., and Mortiboys, H. (2021). Mitochondrial Dysfunction in Alzheimer\u2019s Disease: A Biomarker of the Future?. Biomedicines, 9.","DOI":"10.3390\/biomedicines9010063"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1002\/alz.13835","article-title":"Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer\u2019s disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort","volume":"20","author":"Rudolph","year":"2024","journal-title":"Alzheimers Dement."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/23\/1853\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T11:09:13Z","timestamp":1764068953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/23\/1853"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":119,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cells14231853"],"URL":"https:\/\/doi.org\/10.3390\/cells14231853","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,25]]}}}