{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:25:47Z","timestamp":1791473147080,"version":"4.3.4"},"reference-count":189,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["24-24-00280"],"award-info":[{"award-number":["24-24-00280"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Neurosteroids pregnenolone, progesterone, allopregnanolone, and dehydroepiandrosterone have been actively studied in the last years as candidates for the treatment of neurodegenerative diseases and postinjury rehabilitation. The neuroprotective mechanisms of these neurosteroids have been shown in clinical studies of depression, epilepsy, status epilepticus, traumatic brain injury, fragile X syndrome, and chemical neurotoxicity. However, only the allopregnanolone analogs brexanolone and zuranolone have been recently approved by the FDA for the treatment of depression. The aim of this review was to evaluate whether the endogenous neurosteroids can be used in clinical practice as neuroprotectors. Neurosteroids are multitarget compounds with strong anti-inflammatory, immunomodulatory, and cytoprotective action; they stimulate the synthesis and release of BDNF and increase remyelination and regeneration. In addition to nuclear and membrane steroid hormone receptors, such as PR, mPR, PGRMC1,2, ER, AR, CAR, and PXR, they can bind to GABAA receptors, NMDA receptors, Sigma-1 and -2 receptors (\u03c31-R\/\u03c32-R). Among these, mPRs, PGRMC1,2, sigma receptors, and mitochondrial proteins attract comprehensive attention because of strong binding with the P4 and DHEA, but subsequent signaling is poorly studied. Other plasma membrane and mitochondrial proteins are involved in the rapid nongenomic neuroprotective action of neurosteroids. P-glycoprotein, BCL-2 proteins, and the components of the mitochondrial permeability transition pore (mPTP) play a significant role in the defense against the injuries of the brain and the peripheral nervous system. The role of these proteins in the molecular mechanisms of action in neuroprotection and neuroinflammation has not yet been clearly established. The aspects of their participation in these pathological processes are discussed. New formulations, such as lipophilic emulsions, nanogels, and microneedle array patches, are attractive strategies to overcome the low bioavailability of these neurosteroids for the amelioration and treatment of various nervous disorders.<\/jats:p>","DOI":"10.3390\/ph18070945","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T10:44:41Z","timestamp":1750761881000},"page":"945","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Neurosteroids Progesterone and Dehydroepiandrosterone: Molecular Mechanisms of Action in Neuroprotection and Neuroinflammation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4998-9991","authenticated-orcid":false,"given":"Tatiana A.","family":"Fedotcheva","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Pirogov Russian National Research Medical University, 1 Ostrovityanova St., Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay L.","family":"Shimanovsky","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Pirogov Russian National Research Medical University, 1 Ostrovityanova St., Moscow 117997, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.25259\/SNI_774_2023","article-title":"Neuroprotection: Surgical Approaches in Traumatic Brain Injury","volume":"15","author":"Buccilli","year":"2024","journal-title":"Surg. Neurol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.1097\/JS9.0000000000001466","article-title":"Clot removAl with or without decompRessive Craniectomy under ICP Monitoring for Supratentorial IntraCerebral Hemorrhage (CARICH): A Randomized Controlled Trial","volume":"110","author":"Zhang","year":"2024","journal-title":"Int. J. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mansoor, M., Ibrahim, A., Hamide, A., Tran, T., Candreva, E., and Baltaji, J. (2025). Exercise-Induced Neuroplasticity: Adaptive Mechanisms and Preventive Potential in Neurodegenerative Disorders. Physiologia, 5.","DOI":"10.20944\/preprints202503.0057.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.17691\/stm2023.15.5.04","article-title":"Brain State-Dependent Non-Invasive Neurostimulation with EEG Feedback: Achievements and Prospects","volume":"15","author":"Fedotchev","year":"2023","journal-title":"Sovrem. Tehnol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155635","DOI":"10.1016\/j.phymed.2024.155635","article-title":"Curcumin-Primed Olfactory Mucosa-Derived Mesenchymal Stem Cells Mitigate Cerebral Ischemia\/Reperfusion Injury-Induced Neuronal PANoptosis by Modulating Microglial Polarization","volume":"129","author":"Lan","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1080\/10286020.2024.2371040","article-title":"Mechanisms and Therapeutic Potential of Chinonin in Nervous System Diseases","volume":"26","author":"Hui","year":"2024","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175801","DOI":"10.1016\/j.ejphar.2023.175801","article-title":"A Comparative Study of the Neuroprotective Effects of Dl-3-n-Butylphthalide and Edaravone Dexborneol on Cerebral Ischemic Stroke Rats","volume":"951","author":"Zhang","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jhan, K.-Y., Chen, K.-Y., Chang, P.-K., Chiu, C.-H., Chou, C.-J., and Wang, L.-C. (2025). 7,8-Dihydroxyflavone Provides Neuroprotection and Rescues Behavioral Deficits in Angiostrongylus cantonensis-Infected Mice by Ameliorating Synaptic Loss. J. Microbiol. Immunol. Infect.","DOI":"10.1016\/j.jmii.2025.04.001"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/s41398-023-02514-2","article-title":"Understanding the Mechanism of Action and Clinical Effects of Neuroactive Steroids and GABAergic Compounds in Major Depressive Disorder","volume":"13","author":"Cutler","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kolatorova, L., Vitku, J., Suchopar, J., Hill, M., and Parizek, A. (2022). Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147989"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1056\/NEJMoa1411090","article-title":"A Clinical Trial of Progesterone for Severe Traumatic Brain Injury","volume":"371","author":"Skolnick","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Borowicz, K.K., Piskorska, B., Banach, M., and Czuczwar, S.J. (2011). Neuroprotective Actions of Neurosteroids. Front. Endocrin., 2.","DOI":"10.3389\/fendo.2011.00050"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Guennoun, R. (2020). Progesterone in the Brain: Hormone, Neurosteroid and Neuroprotectant. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155271"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100314","DOI":"10.1016\/j.coemr.2021.100314","article-title":"Neurosteroids and Neuropathic Pain: An up-to-Date Perspective","volume":"22","author":"Ferreyra","year":"2022","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105916","DOI":"10.1016\/j.neuint.2024.105916","article-title":"Neurosteroids and Translocator Protein (TSPO) in Neuroinflammation","volume":"182","author":"Angeloni","year":"2025","journal-title":"Neurochem. Int."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Mallah, K., Couch, C., Borucki, D.M., Toutonji, A., Alshareef, M., and Tomlinson, S. (2020). Anti-Inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go from Here?. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.02021"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Yilmaz, C., Karali, K., Fodelianaki, G., Gravanis, A., Chavakis, T., Charalampopoulos, I., and Alexaki, V.I. (2019). Neurosteroids as Regulators of Neuroinflammation. Front. Neuroendocrinol., 55.","DOI":"10.1016\/j.yfrne.2019.100788"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.jsbmb.2014.09.001","article-title":"Progesterone and Allopregnanolone in the Central Nervous System: Response to Injury and Implication for Neuroprotection","volume":"146","author":"Guennoun","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Sohan, M.S.R., Hossain, M.F., Hossain, S., Omori, Y., Amin, M.T., Hasan, M.E., and Tokumoto, T. (2025). Biochemical Characterization of Zebrafish Paqr5b. Biochem. Biophys. Rep., 42.","DOI":"10.1016\/j.bbrep.2025.101994"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mathouchanh, M., and Lessman, C.A. (2025). Effects of Progestogen Neurosteroids on Locomotor Activity in Zebrafish Embryos and Larvae. Fish. Physiol. Biochem., 51.","DOI":"10.1007\/s10695-025-01519-6"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12220","DOI":"10.1074\/jbc.RA119.008875","article-title":"Metabotropic, but Not Allosteric, Effects of Neurosteroids on GABAergic Inhibition Depend on the Phosphorylation of GABAA Receptors","volume":"294","author":"Parakala","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Raciti, L., Formica, C., Raciti, G., Quartarone, A., and Calabr\u00f2, R.S. (2023). Gender and Neurosteroids: Implications for Brain Function, Neuroplasticity and Rehabilitation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054758"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/B978-0-444-53630-3.00008-7","article-title":"Neurosteroids","volume":"Volume 186","author":"Reddy","year":"2010","journal-title":"Progress in Brain Research"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.tips.2016.04.003","article-title":"Clinical Potential of Neurosteroids for CNS Disorders","volume":"37","author":"Reddy","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Tuem, K.B., and Atey, T.M. (2017). Neuroactive Steroids: Receptor Interactions and Responses. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00442"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s00540-023-03291-4","article-title":"Neurosteroids and Their Potential as a Safer Class of General Anesthetics","volume":"38","author":"Tateiwa","year":"2024","journal-title":"J. Anesth."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ygcen.2015.09.030","article-title":"Neurosteroids; Potential Underpinning Roles in Maintaining Homeostasis","volume":"225","author":"Rahmani","year":"2016","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1210\/er.2015-1036","article-title":"The Regulation of Steroid Action by Sulfation and Desulfation","volume":"36","author":"Mueller","year":"2015","journal-title":"Endocr. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41386-023-01626-z","article-title":"Neurosteroids: Mechanistic Considerations and Clinical Prospects","volume":"49","author":"Maguire","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1126\/science.2422758","article-title":"Steroid Hormone Metabolites Are Barbiturate-like Modulators of the GABA Receptor","volume":"232","author":"Majewska","year":"1986","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1002\/hbm.22399","article-title":"The Neurosteroids Allopregnanolone and Dehydroepiandrosterone Modulate Resting-State Amygdala Connectivity: Neurosteroids Modulate Amygdala Resting fcMRI","volume":"35","author":"Sripada","year":"2014","journal-title":"Hum. Brain Mapp."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.yfrne.2008.11.002","article-title":"Neurobiological and Neuropsychiatric Effects of Dehydroepiandrosterone (DHEA) and DHEA Sulfate (DHEAS)","volume":"30","author":"Maninger","year":"2009","journal-title":"Front. Neuroendocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4089","DOI":"10.1073\/pnas.95.8.4089","article-title":"Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulfate (DHEAS) as Neuroactive Neurosteroids","volume":"95","author":"Baulieu","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1124\/jpet.123.001816","article-title":"Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic","volume":"388","author":"Reddy","year":"2024","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/jnc.15503","article-title":"Neurosteroids: A Novel Promise for the Treatment of Stroke and Post-stroke Complications","volume":"160","author":"Xu","year":"2022","journal-title":"J. Neurochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"177446","DOI":"10.1016\/j.ejphar.2025.177446","article-title":"The Influence of Chronic or Acute DHEA Exposure on \u03b2-Endorphin Levels in the Nucleus Accumbens","volume":"996","author":"Doron","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev-med-050423-095712","article-title":"Transformative Therapies for Depression: Postpartum Depression, Major Depressive Disorder, and Treatment-Resistant Depression","volume":"76","author":"Richardson","year":"2025","journal-title":"Annu. Rev. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mayer, E., Winkler, I., Huber, E., Urbanek, M., Kiechl-Kohlendorfer, U., Griesmaier, E., and Posod, A. (2024). Effects of DHEA and DHEAS in Neonatal Hypoxic\u2013Ischemic Brain Injury. Antioxidants, 13.","DOI":"10.20944\/preprints202410.2113.v1"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.steroids.2018.02.005","article-title":"Androst-5-Ene-3\u03b2,7\u03b1\/\u03b2,17\u03b2-Triols, Their Plasma Levels and Dependence on the Hypothalamic\u2013Pituitary\u2013Adrenal Axis","volume":"134","author":"Hill","year":"2018","journal-title":"Steroids"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e39027","DOI":"10.1097\/MD.0000000000039027","article-title":"A Phase 2, Open-Label Study of Anti-Inflammatory NE3107 in Patients with Dementias","volume":"103","author":"Haroon","year":"2024","journal-title":"Medicine"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Georgelou, K., Saridaki, E.-A., Karali, K., Papagiannaki, A., Charalampopoulos, I., Gravanis, A., and Tzeranis, D.S. (2023). Microneurotrophin BNN27 Reduces Astrogliosis and Increases Density of Neurons and Implanted Neural Stem Cell-Derived Cells after Spinal Cord Injury. Biomedicines, 11.","DOI":"10.3390\/biomedicines11041170"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1089\/089771503765355531","article-title":"A Novel Dehydroepiandrosterone Analog Improves Functional Recovery in a Rat Traumatic Brain Injury Model","volume":"20","author":"Malik","year":"2003","journal-title":"J. Neurotrauma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e70031","DOI":"10.1002\/prp2.70031","article-title":"Mechanisms and Pharmacotherapy of Cancer Cachexia-associated Anorexia","volume":"13","author":"Sato","year":"2025","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ulchenko, D., Miloykovich, L., Zemlyanaya, O., Shimanovsky, N., and Fedotcheva, T. (2023). Possible Participation of Adenine Nucleotide Translocase ANT1 in the Cytotoxic Action of Progestins, Glucocorticoids, and Diclofenac on Tumor Cells. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15122787"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/j.1399-6576.1994.tb03987.x","article-title":"Pharmacokinetics and Pharmacodynamics of Eltanolone (Pregnanolone), a New Steroid Intravenous Anaesthetic, in Humans","volume":"38","author":"Carl","year":"1994","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e200287","DOI":"10.1001\/jamanetworkopen.2020.0287","article-title":"Effect of Pregnenolone vs Placebo on Self-Reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial","volume":"3","author":"Naylor","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1016\/S0140-6736(18)31551-4","article-title":"Brexanolone Injection in Post-Partum Depression: Two Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase 3 Trials","volume":"392","author":"Colquhoun","year":"2018","journal-title":"Lancet"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s13311-017-0555-6","article-title":"Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor\/Ataxia Syndrome","volume":"14","author":"Wang","year":"2017","journal-title":"Neurotherapeutics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"388","DOI":"10.2174\/0929867330666230320123952","article-title":"Ganaxolone: First FDA-Approved Medicine for the Treatment ofSeizures Associated with Cyclin-Dependent Kinase-like 5 DeficiencyDisorder","volume":"31","author":"De","year":"2024","journal-title":"Curr. Med. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.psyneuen.2017.02.031","article-title":"Treatment of Premenstrual Dysphoric Disorder with the GABA A Receptor Modulating Steroid Antagonist Sepranolone (UC1010)\u2014A Randomized Controlled Trial","volume":"80","author":"Bixo","year":"2017","journal-title":"Psychoneuroendocrinology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/s41386-023-01751-9","article-title":"Efficacy and Safety of Zuranolone Co-Initiated with an Antidepressant in Adults with Major Depressive Disorder: Results from the Phase 3 CORAL Study","volume":"49","author":"Parikh","year":"2024","journal-title":"Neuropsychopharmacology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"23m14845","DOI":"10.4088\/JCP.23m14845","article-title":"Long-Term Safety and Efficacy of Initial and Repeat Treatment Courses with Zuranolone in Adult Patients with Major Depressive Disorder: Interim Results From the Open-Label, Phase 3 SHORELINE Study","volume":"85","author":"Cutler","year":"2023","journal-title":"J. Clin. Psychiatry"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Marecki, R., Ka\u0142uska, J., Kolanek, A., Haka\u0142o, D., and Waszkiewicz, N. (2023). Zuranolone\u2013Synthetic Neurosteroid in Treatment of Mental Disorders: Narrative Review. Front. Psychiatry, 14.","DOI":"10.3389\/fpsyt.2023.1298359"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Qiu, Y., Tao, Y., Duan, A., Wei, X., Wang, M., Xie, M., Chen, Z., Shang, J., and Wang, Z. (2024). Efficacy and Tolerability of Zuranolone in Patients with Depression: A Meta-Analysis of Randomized Controlled Trials. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1334694"},{"key":"ref_55","first-page":"e65866","article-title":"The Emerging Role of Neurosteroids: Novel Drugs Brexanalone, Sepranolone, Zuranolone, and Ganaxolone in Mood and Neurological Disorders","volume":"16","author":"Singhal","year":"2024","journal-title":"Cureus"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Fedotcheva, T.A., Uspenskaya, M.E., Ulchenko, D.N., and Shimanovsky, N.L. (2024). Dehydroepiandrosterone and Its Metabolite 5-Androstenediol: New Therapeutic Targets and Possibilities for Clinical Application. Pharmaceuticals, 17.","DOI":"10.3390\/ph17091186"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tomczyk, K., Chmaj-Wierzchowska, K., Wszo\u0142ek, K., and Wilczak, M. (2023). New Possibilities for Hormonal Vaginal Treatment in Menopausal Women. J. Clin. Med., 12.","DOI":"10.3390\/jcm12144740"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"qdae002.236","DOI":"10.1093\/jsxmed\/qdae002.236","article-title":"(273) Influences of Oral Dehydroepiandrosterone (DHEA) Administration on Hormonal Profile, Menopausal Clinical Symptoms and Sexual Function in Early Postmenopausal Symptomatic Women","volume":"21","author":"Andguladze","year":"2024","journal-title":"J. Sex. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.beem.2004.02.006","article-title":"Dehydroepiandrosterone and Ageing","volume":"18","author":"Arlt","year":"2004","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Dutheil, F., De Saint Vincent, S., Pereira, B., Schmidt, J., Moustafa, F., Charkhabi, M., Bouillon-Minois, J.-B., and Clinchamps, M. (2021). DHEA as a Biomarker of Stress: A Systematic Review and Meta-Analysis. Front. Psychiatry, 12.","DOI":"10.3389\/fpsyt.2021.688367"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"21379","DOI":"10.1074\/jbc.M200491200","article-title":"Dehydroepiandrosterone Activates Endothelial Cell Nitric-Oxide Synthase by a Specific Plasma Membrane Receptor Coupled to G\u03b1i2,3","volume":"277","author":"Liu","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Erceg, N., Micic, M., Forouzan, E., and Knezevic, N.N. (2025). The Role of Cortisol and Dehydroepiandrosterone in Obesity, Pain, and Aging. Diseases, 13.","DOI":"10.3390\/diseases13020042"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Karakus, E., Schmid, A., Sch\u00e4ffler, A., Wudy, S.A., and Geyer, J. (2025). Intracrine Formation of Steroid Hormones in Breast Cancer, Epidermal Keratinocyte, Dermal Fibroblast, and Adipocyte Cell Lines Measured by LC-MS\/MS. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031188"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.molimm.2020.12.023","article-title":"Dehydroepiandrosterone attenuates LPS-induced inflammatory responses via activation of Nrf2 in RAW264.7 macrophages","volume":"131","author":"Cao","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_65","first-page":"757432","article-title":"5-androstenediol ameliorates pleurisy, septic shock, and experimental autoimmune encephalomyelitis in mice","volume":"2010","author":"Nicoletti","year":"2010","journal-title":"Autoimmune Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"423","DOI":"10.14336\/AD.2021.0913","article-title":"Dehydroepiandrosterone, Cancer, and Aging","volume":"13","author":"Schwartz","year":"2022","journal-title":"Aging Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"61","DOI":"10.18413\/rrpharmacology.9.10015","article-title":"The endogenic neurosteroid system and its role in the pathogenesis and therapy of mental disorders","volume":"9","author":"Bairamova","year":"2023","journal-title":"Res. Results Pharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Garcia, M., Thirouard, L., Sed\u00e8s, L., Monrose, M., Holota, H., Caira, F., Volle, D.H., and Beaudoin, C. (2018). Nuclear Receptor Metabolism of Bile Acids and Xenobiotics: A Coordinated Detoxification System with Impact on Health and Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113630"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1124\/dmd.107.016303","article-title":"Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor","volume":"35","author":"Kohalmy","year":"2007","journal-title":"Drug Metab. Dispos."},{"key":"ref_70","first-page":"S107","article-title":"High Bioavailability of Dehydroepiandrosterone Administered Percutaneously in the Rat","volume":"150","author":"Labrie","year":"1996","journal-title":"J. Endocrinol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"114370","DOI":"10.1016\/j.expneurol.2023.114370","article-title":"Pregnenolone for the Treatment of L-DOPA-Induced Dyskinesia in Parkinson\u2019s Disease","volume":"363","author":"Corsi","year":"2023","journal-title":"Exp. Neurol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e05180","DOI":"10.1016\/j.heliyon.2020.e05180","article-title":"Long-Term Supplementation of Dehydroepiandrosterone Improved Depressive-like Behaviors by Increasing BDNF Expression in the Hippocampus in Ovariectomized Rats","volume":"6","author":"Wu","year":"2020","journal-title":"Heliyon"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Cao, T., Tang, M., Jiang, P., Zhang, B., Wu, X., Chen, Q., Zeng, C., Li, N., Zhang, S., and Cai, H. (2021). A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.612083"},{"key":"ref_74","first-page":"506191","article-title":"Dehydroepiandrosterone Stimulates Nerve Growth Factor and Brain Derived Neurotrophic Factor in Cortical Neurons","volume":"2013","author":"Rahmani","year":"2013","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_75","first-page":"1046","article-title":"The Effects of Progesterone on Glial Cell Line-derived Neurotrophic Factor Secretion from C6 Glioma Cells","volume":"15","author":"Hassanzadeh","year":"2012","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3202","DOI":"10.1073\/pnas.0307325101","article-title":"Mitotic and Neurogenic Effects of Dehydroepiandrosterone (DHEA) on Human Neural Stem Cell Cultures Derived from the Fetal Cortex","volume":"101","author":"Suzuki","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Perugini, J., Di Mercurio, E., Giuliani, A., Sabbatinelli, J., Bonfigli, A.R., Tortato, E., Severi, I., Cinti, S., Olivieri, F., and Le Roux, C.W. (2022). Ciliary Neurotrophic Factor Is Increased in the Plasma of Patients with Obesity and Its Levels Correlate with Diabetes and Inflammation Indices. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-11942-x"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.psyneuen.2018.09.038","article-title":"Ciliary Neurotrophic Factor Is a Key Sex-Specific Regulator of Depressive-like Behavior in Mice","volume":"100","author":"Jia","year":"2019","journal-title":"Psychoneuroendocrinology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"93","DOI":"10.17691\/stm2021.13.1.11","article-title":"Clinical Use of Progestins and Their Mechanisms of Action: Present and Future (Review)","volume":"13","author":"Fedotcheva","year":"2021","journal-title":"Sovrem. Tekhnologii Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eplepsyres.2009.02.017","article-title":"The Role of Neurosteroids in the Pathophysiology and Treatment of Catamenial Epilepsy","volume":"85","author":"Reddy","year":"2009","journal-title":"Epilepsy Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Frye, C.A., Cleveland, D.M., Sadarangani, A., and Torgersen, J.K. (2025). Progesterone Promotes Anti-Anxiety\/Depressant-like Behavior and Trophic Actions of BDNF in the Hippocampus of Female Nuclear Progesterone Receptor, but Not 5\u03b1-Reductase, Knockout Mice. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031173"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/j.0013-9580.2003.59402.x","article-title":"The Anticonvulsant Effects of Progesterone and 5\u03b1-dihydroprogesterone on Amygdala-kindled Seizures in Rats","volume":"44","author":"Burnham","year":"2003","journal-title":"Epilepsia"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0306-4530(03)00033-7","article-title":"Administration of Progesterone Produces Mild Sedative-like Effects in Men and Women","volume":"29","author":"Lindsey","year":"2004","journal-title":"Psychoneuroendocrinology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.seizure.2007.11.014","article-title":"Catamenial Epilepsy: Definition, Prevalence Pathophysiology and Treatment","volume":"17","author":"Herzog","year":"2008","journal-title":"Seizure"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.seizure.2015.02.024","article-title":"Catamenial Epilepsy: Update on Prevalence, Pathophysiology and Treatment from the Findings of the NIH Progesterone Treatment Trial","volume":"28","author":"Herzog","year":"2015","journal-title":"Seizure"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1111\/epi.12969","article-title":"Distribution of Seizures across the Menstrual Cycle in Women with Epilepsy","volume":"56","author":"Herzog","year":"2015","journal-title":"Epilepsia"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Dreven\u0161ek, G. (2018). New Insights for Hormone Therapy in Perimenopausal Women Neuroprotection. Sex Hormones in Neurodegenerative Processes and Diseases, InTech.","DOI":"10.5772\/66585"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.tem.2022.10.001","article-title":"Many or Too Many Progesterone Membrane Receptors? Clinical Implications","volume":"33","author":"Wendler","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1126\/science.aad6887","article-title":"Unconventional Endocannabinoid Signaling Governs Sperm Activation via the Sex Hormone Progesterone","volume":"352","author":"Miller","year":"2016","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/humrep\/dey377","article-title":"A Novel Copy Number Variation in CATSPER2 Causes Idiopathic Male Infertility with Normal Semen Parameters","volume":"34","author":"Luo","year":"2019","journal-title":"Human. Reprod."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Castelnovo, L.F., and Thomas, P. (2023). Progesterone Exerts a Neuroprotective Action in a Parkinson\u2019s Disease Human Cell Model through Membrane Progesterone Receptor \u03b1 (mPR\u03b1\/PAQR7). Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1125962"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.pneurobio.2013.09.004","article-title":"Revisiting the Roles of Progesterone and Allopregnanolone in the Nervous System: Resurgence of the Progesterone Receptors","volume":"113","author":"Schumacher","year":"2014","journal-title":"Progress Neurobiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Fedotcheva, T.A., Fedotcheva, N.I., and Shimanovsky, N.L. (2021). Progestins as Anticancer Drugs and Chemosensitizers, New Targets and Applications. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13101616"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/imm.13004","article-title":"Impact of Sex Hormones on Immune Function and Multiple Sclerosis Development","volume":"156","author":"Ysrraelit","year":"2019","journal-title":"Immunology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/mi.2017.35","article-title":"Progesterone-Based Compounds Affect Immune Responses and Susceptibility to Infections at Diverse Mucosal Sites","volume":"10","author":"Hall","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Singh, M., Krishnamoorthy, V.R., Kim, S., Khurana, S., and LaPorte, H.M. (2024). Brain-Derived Neuerotrophic Factor and Related Mechanisms That Mediate and Influence Progesterone-Induced Neuroprotection. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1286066"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.maturitas.2003.09.021","article-title":"Differential Effects of Progestins on the Brain","volume":"46","author":"Gruber","year":"2003","journal-title":"Maturitas"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0039-128X(00)00173-2","article-title":"Progesterone as a Neuroactive Neurosteroid, with Special Reference to the Effect of Progesterone on Myelination","volume":"65","author":"Baulieu","year":"2000","journal-title":"Steroids"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11910-023-01326-7","article-title":"Hormonal Therapies in Multiple Sclerosis: A Review of Clinical Data","volume":"24","author":"Hsu","year":"2024","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Almeida, F.B., Barros, H.M.T., and Pinna, G. (2021). Neurosteroids and Neurotrophic Factors: What Is Their Promise as Biomarkers for Major Depression and PTSD?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041758"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2470547018818555","DOI":"10.1177\/2470547018818555","article-title":"Overview of the Molecular Steps in Steroidogenesis of the GABAergic Neurosteroids Allopregnanolone and Pregnanolone","volume":"2","author":"Liang","year":"2018","journal-title":"Chronic Stress."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Hirtz, A., Rech, F., Dubois-Pot-Schneider, H., and Dumond, H. (2020). Astrocytoma: A Hormone-Sensitive Tumor?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239114"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Balan, I., Boero, G., Ch\u00e9ry, S.L., McFarland, M.H., Lopez, A.G., and Morrow, A.L. (2024). Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders. Life, 14.","DOI":"10.3390\/life14050582"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1038\/npp.2009.26","article-title":"Proof-of-Concept Trial with the Neurosteroid Pregnenolone Targeting Cognitive and Negative Symptoms in Schizophrenia","volume":"34","author":"Marx","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/pcn.12150","article-title":"Pregnenolone Treatment Reduces Severity of Negative Symptoms in Recent-onset Schizophrenia: An 8-week, Double-blind, Randomized Add-on Two-center Trial","volume":"68","author":"Ritsner","year":"2014","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1038\/npp.2014.138","article-title":"A Randomized, Double-Blind, Placebo-Controlled Trial of Pregnenolone for Bipolar Depression","volume":"39","author":"Brown","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1007\/s10803-014-2144-4","article-title":"Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder","volume":"44","author":"Fung","year":"2014","journal-title":"J. Autism Dev. Disord."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Gao, H., Magin, Z., Fogelman, N., Sinha, R., Angarita, G.A., and Milivojevic, V. (2024). Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings. Life, 14.","DOI":"10.3390\/life14111483"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Morrow, A.L., Boero, G., and Balan, I. (2024). Emerging Evidence for Endogenous Neurosteroid Modulation of Pro-Inflammatory and Anti-Inflammatory Pathways That Impact Neuropsychiatric Disease. Neurosci. Biobehav. Rev., 158.","DOI":"10.1016\/j.neubiorev.2024.105558"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s10194-021-01231-9","article-title":"Comparison of Pregnenolone Sulfate, Pregnanolone and Estradiol Levels between Patients with Menstrually-Related Migraine and Controls: An Exploratory Study","volume":"22","author":"Rustichelli","year":"2021","journal-title":"J. Headache Pain."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s10194-023-01687-x","article-title":"Progesterone Distribution in the Trigeminal System and Its Role to Modulate Sensory Neurotransmission: Influence of Sex","volume":"24","author":"Maddahi","year":"2023","journal-title":"J. Headache Pain."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Pinna, G. (2020). Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00236"},{"key":"ref_113","unstructured":"(2025, April 07). Available online: https:\/\/www.kegg.jp\/entry\/D11149."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"D1465","DOI":"10.1093\/nar\/gkad751","article-title":"TTD: Therapeutic Target Database Describing Target Druggability Information","volume":"52","author":"Zhou","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1007\/s40265-022-01724-0","article-title":"Ganaxolone: First Approval","volume":"82","author":"Lamb","year":"2022","journal-title":"Drugs"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e12258","DOI":"10.1002\/trc2.12258","article-title":"Exploratory Imaging Outcomes of a Phase 1b\/2a Clinical Trial of Allopregnanolone as a Regenerative Therapeutic for Alzheimer\u2019s Disease: Structural Effects and Functional Connectivity Outcomes","volume":"8","author":"Raikes","year":"2022","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sethi, R., G\u00f3mez-Coronado, N., Walker, A.J., Robertson, O.D., Agustini, B., Berk, M., and Dodd, S. (2019). Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders. Front. Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00605"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Pavlik, T.I., Shimanovsky, N.L., Zemlyanaya, O.A., and Fedotcheva, T.A. (2023). The Effect of Progestins on Cytokine Production in the Peripheral Blood Mononuclear Cells of Menopausal Women and Their Luminol-Dependent Chemiluminescence. Molecules, 28.","DOI":"10.3390\/molecules28114354"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s12028-016-0342-y","article-title":"Progesterone Provides the Pleiotropic Neuroprotective Effect on Traumatic Brain Injury Through the Nrf2\/ARE Signaling Pathway","volume":"26","author":"Zhang","year":"2017","journal-title":"Neurocrit. Care"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Lucchi, C., Codeluppi, A., Filaferro, M., Vitale, G., Rustichelli, C., Avallone, R., Mandrioli, J., and Biagini, G. (2023). Human Microglia Synthesize Neurosteroids to Cope with Rotenone-Induced Oxidative Stress. Antioxidants, 12.","DOI":"10.3390\/antiox12040963"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"O\u2019Connor, J.L., and Nissen, J.C. (2023). The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054739"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Fedotcheva, T.A., Fedotcheva, N.I., and Shimanovsky, N.L. (2022). Progesterone as an Anti-Inflammatory Drug and Immunomodulator: New Aspects in Hormonal Regulation of the Inflammation. Biomolecules, 12.","DOI":"10.3390\/biom12091299"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3359","DOI":"10.2174\/092986709789057653","article-title":"Translocator Protein Ligands as Promising Therapeutic Tools for Anxiety Disorders","volume":"16","author":"Taliani","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s00018-024-05544-1","article-title":"18 kDa TSPO Targeting Drives Polarized Human Microglia towards a Protective and Restorative Neurosteroidome Profile","volume":"82","author":"Germelli","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"112631","DOI":"10.1016\/j.bbr.2020.112631","article-title":"Ketamine\u2019s Dose Related Multiple Mechanisms of Actions: Dissociative Anesthetic to Rapid Antidepressant","volume":"390","author":"Lavender","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3803","DOI":"10.1007\/s12035-020-01988-1","article-title":"The Sigma-2 Receptor\/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of A\u03b242 and Its Protein Aggregates","volume":"57","author":"Riad","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1517\/17425255.2012.658367","article-title":"S2RPgrmc1: The Cytochrome-Related Sigma-2 Receptor That Regulates Lipid and Drug Metabolism and Hormone Signaling","volume":"8","author":"Ahmed","year":"2012","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.14283\/jpad.2024.154","article-title":"A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer\u2019s Disease","volume":"11","author":"Vijverberg","year":"2024","journal-title":"J. Prev. Alzheimers Dis."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Steinfield, S.R., Stenn, D.F., Chen, H., and Kalisch, B.E. (2025). A Review of the Clinical Progress of CT1812, a Novel Sigma-2 Receptor Antagonist for the Treatment of Alzheimer\u2019s Disease. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050659"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Kelp, N.C., Pru, C.A., Paudel, S., Lydon, J.P., Kim, J.J., Peluso, J.J., and Pru, J.K. (2025). Uterine Pgrmc2 Deficiency Attenuates Endometrial Hyperplasia and Cancer and Prolongs Lifespan in a Pten Loss-of-Function-Induced Cancer Model. Cancers, 17.","DOI":"10.3390\/cancers17071178"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1055\/s-0043-113635","article-title":"High Level of Progesteron Receptor Membrane Component 1 (PGRMC 1) in Tissue of Breast Cancer Patients Is Associated with Worse Response to Anthracycline-Based Neoadjuvant Therapy","volume":"49","author":"Willibald","year":"2017","journal-title":"Horm. Metab. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1111\/cns.14122","article-title":"Gain-of-function of Progesterone Receptor Membrane Component 2 Ameliorates Ischemic Brain Injury","volume":"29","author":"Zhou","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.tips.2016.01.003","article-title":"The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems","volume":"37","author":"Su","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1038\/s41467-024-49894-7","article-title":"Insight into Binding of Endogenous Neurosteroid Ligands to the Sigma-1 Receptor","volume":"15","author":"Fu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pneurobio.2012.09.001","article-title":"Sigma-1 receptor chaperone and brain-derived neurotrophic factor: Emerging links between cardiovascular disease and depression","volume":"100","author":"Hashimoto","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jphs.2014.11.010","article-title":"Activation of Sigma-1 Receptor Chaperone in the Treatment of Neuropsychiatric Diseases and Its Clinical Implication","volume":"127","author":"Hashimoto","year":"2015","journal-title":"J. Pharmacol. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"17448069211069255","DOI":"10.1177\/17448069211069255","article-title":"Sigma-1 Receptors and Progesterone Metabolizing Enzymes in Nociceptive Sensory Neurons of the Female Rat Trigeminal Ganglia: A Neural Substrate for the Antinociceptive Actions of Progesterone","volume":"18","author":"Hornung","year":"2022","journal-title":"Mol. Pain."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"875","DOI":"10.2174\/138161212799436476","article-title":"Sigma-1 Receptor Agonists as Therapeutic Drugs for Cognitive Impairment in Neuropsychiatric Diseases","volume":"18","author":"Niitsu","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Ryskamp, D.A., Korban, S., Zhemkov, V., Kraskovskaya, N., and Bezprozvanny, I. (2019). Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00862"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Moriguchi, S., Shinoda, Y., Yamamoto, Y., Sasaki, Y., Miyajima, K., Tagashira, H., and Fukunaga, K. (2013). Stimulation of the Sigma-1 Receptor by DHEA Enhances Synaptic Efficacy and Neurogenesis in the Hippocampal Dentate Gyrus of Olfactory Bulbectomized Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060863"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5649","DOI":"10.1007\/s12035-021-02524-5","article-title":"Emerging Benefits: Pathophysiological Functions and Target Drugs of the Sigma-1 Receptor in Neurodegenerative Diseases","volume":"58","author":"Wu","year":"2021","journal-title":"Mol. Neurobiol."},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Yang, K., Zeng, C., Wang, C., Sun, M., Yin, D., and Sun, T. (2020). Sigma-2 Receptor\u2014A Potential Target for Cancer\/Alzheimer\u2019s Disease Treatment via Its Regulation of Cholesterol Homeostasis. Molecules, 25.","DOI":"10.3390\/molecules25225439"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1021\/acschemneuro.8b00543","article-title":"Neuroprotective Efficacy of a Sigma 2 Receptor\/TMEM97 Modulator (DKR-1677) after Traumatic Brain Injury","volume":"10","author":"Watson","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Wang, H., Peng, Z., Li, Y., Sahn, J.J., Hodges, T.R., Chou, T.-H., Liu, Q., Zhou, X., Jiao, S., and Porciatti, V. (2022). \u03c32R\/TMEM97 in Retinal Ganglion Cell Degeneration. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-24537-3"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"113659","DOI":"10.1016\/j.jconrel.2025.113659","article-title":"Delivery of a Novel Neuroprotective Compound to the Retina in Rat and Rabbit Animal Models","volume":"382","author":"Garrett","year":"2025","journal-title":"J. Control Release"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.3233\/JAD-230994","article-title":"CT1812, a Small Molecule Sigma-2 Receptor Antagonist for Alzheimer\u2019s Disease Treatment: A Systematic Review of Available Clinical Data","volume":"101","author":"Thitilertdecha","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13195-024-01382-2","article-title":"A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer\u2019s disease","volume":"16","author":"Mecca","year":"2024","journal-title":"Alzheimers Res. Ther."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s40035-023-00358-w","article-title":"A Phase 1b Randomized Clinical Trial of CT1812 to Measure A\u03b2 Oligomer Displacement in Alzheimer\u2019s Disease Using an Indwelling CSF Catheter","volume":"12","author":"LaBarbera","year":"2023","journal-title":"Transl. Neurodegener."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Dierckx, R.A.J.O., Otte, A., De Vries, E.F.J., Van Waarde, A., and Lammertsma, A.A. (2021). Sigma-2 Receptors: An Emerging Target for CNS PET Imaging Studies. PET and SPECT of Neurobiological Systems, Springer International Publishing.","DOI":"10.1007\/978-3-030-53176-8"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Lizama, B.N., Kahle, J., Catalano, S.M., Caggiano, A.O., Grundman, M., and Hamby, M.E. (2023). Sigma-2 Receptors\u2014From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076251"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1186\/s13054-023-04538-y","article-title":"Cerebral Apolipoprotein E and Amyloid Precursor-like Protein 1 as Risk Factors for Chronic Neurodegeneration after Non-Traumatic Acute Brain Injury (ABI)","volume":"27","author":"Santacruz","year":"2023","journal-title":"Crit. Care"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Izzo, N.J., Xu, J., Zeng, C., Kirk, M.J., Mozzoni, K., Silky, C., Rehak, C., Yurko, R., Look, G., and Rishton, G. (2014). Alzheimer\u2019s Therapeutics Targeting Amyloid Beta 1\u201342 Oligomers II: Sigma-2\/PGRMC1 Receptors Mediate Abeta 42 Oligomer Binding and Synaptotoxicity. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111899"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1210\/en.2007-1050","article-title":"Progesterone Receptor Membrane Component-1 (PGRMC1) Is the Mediator of Progesterone\u2019s Antiapoptotic Action in Spontaneously Immortalized Granulosa Cells as Revealed by PGRMC1 Small Interfering Ribonucleic Acid Treatment and Functional Analysis of PGRMC1 Mutations","volume":"149","author":"Peluso","year":"2008","journal-title":"Endocrinology"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.1210\/en.2008-1447","article-title":"Progesterone Increases Rat Neural Progenitor Cell Cycle Gene Expression and Proliferation Via Extracellularly Regulated Kinase and Progesterone Receptor Membrane Components 1 and 2","volume":"150","author":"Liu","year":"2009","journal-title":"Endocrinology"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrd753","article-title":"Pxr, Car and Drug Metabolism","volume":"1","author":"Willson","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s00280-009-1221-4","article-title":"PXR-Mediated Induction of P-Glycoprotein by Anticancer Drugs in a Human Colon Adenocarcinoma-Derived Cell Line","volume":"66","author":"Harmsen","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Frye, C.A., Koonce, C.J., and Walf, A.A. (2014). Novel Receptor Targets for Production and Action of Allopregnanolone in the Central Nervous System: A Focus on Pregnane Xenobiotic Receptor. Front. Cell. Neurosci., 8.","DOI":"10.3389\/fncel.2014.00106"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"13807","DOI":"10.1073\/pnas.0606218103","article-title":"Pregnane X Receptor (PXR) Activation: A Mechanism for Neuroprotection in a Mouse Model of Niemann\u2013Pick C Disease","volume":"103","author":"Langmade","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Thejer, B.M., Infantino, V., Santarsiero, A., Pappalardo, I., Abatematteo, F.S., Teakel, S., Van Oosterum, A., Mach, R.H., Denora, N., and Lee, B.C. (2023). Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076381"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1007\/s00406-022-01532-3","article-title":"Neurosteroids and Translocator Protein 18 kDa (TSPO) in Depression: Implications for Synaptic Plasticity, Cognition, and Treatment Options","volume":"273","author":"Rupprecht","year":"2023","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1080\/15622975.2021.1961503","article-title":"Neuroinflammation and Psychiatric Disorders: Relevance of C1q, Translocator Protein (18 kDa) (TSPO), and Neurosteroids","volume":"23","author":"Rupprecht","year":"2022","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2174\/1567205017666200217105950","article-title":"A Protective Role of Translocator Protein in Alzheimer\u2019s Disease Brain","volume":"17","author":"Jung","year":"2020","journal-title":"Curr. Alzheimer Res."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Seidlmayer, L.K., Hanson, B.J., Thai, P.N., Schaefer, S., Bers, D.M., and Dedkova, E.N. (2021). PK11195 Protects from Cell Death Only When Applied During Reperfusion: Succinate-Mediated Mechanism of Action. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.628508"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Wang, J., and Beecher, K. (2021). TSPO: An Emerging Role in Appetite for a Therapeutically Promising Biomarker. Open Biol., 11.","DOI":"10.1098\/rsob.210173"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1021\/acschemneuro.2c00582","article-title":"Targeting TSPO Reduces Inflammation and Apoptosis in an In Vitro Photoreceptor-Like Model of Retinal Degeneration","volume":"13","author":"Corsi","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12974-018-1324-0","article-title":"Central Intracrine DHEA Synthesis in Ageing-Related Neuroinflammation and Neurodegeneration: Therapeutic Potential?","volume":"15","author":"Powrie","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Li, Y., Sun, J., Wu, R., Bai, J., Hou, Y., Zeng, Y., Zhang, Y., Wang, X., Wang, Z., and Meng, X. (2020). Mitochondrial MPTP: A Novel Target of Ethnomedicine for Stroke Treatment by Apoptosis Inhibition. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00352"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/ddr.21593","article-title":"Pharmacology of Mitochondrial Permeability Transition Pore Inhibitors","volume":"80","author":"Naryzhnaya","year":"2019","journal-title":"Drug Dev. Res."},{"key":"ref_169","first-page":"787","article-title":"Progesterone Induced Neuroprotection in Reperfusion Promoted Mitochondrial Dysfunction Following Focal Cerebral Ischemia in Rats","volume":"10","author":"Andrabi","year":"2017","journal-title":"Dis. Models Mech."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/s41418-023-01187-0","article-title":"Identity, Structure, and Function of the Mitochondrial Permeability Transition Pore: Controversies, Consensus, Recent Advances, and Future Directions","volume":"30","author":"Bernardi","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.bcp.2009.05.028","article-title":"Effect of Progesterone and Its Synthetic Analogues on the Activity of Mitochondrial Permeability Transition Pore in Isolated Rat Liver Mitochondria","volume":"78","author":"Fedotcheva","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Andrianova, N.V., Brezgunova, A.A., Buyan, M.I., Makievskaya, C.I., Buyan, A.I., Cherkesova, K.S., Pevzner, I.B., Zorova, L.D., Zorov, D.B., and Plotnikov, E.Y. (2024). Sex-Specific Effects of Estradiol and Progesterone in Ischemic Kidney Injury. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063155"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1089\/neu.2018.5706","article-title":"Neuroprotective Effects of Cyclosporine in a Porcine Pre-Clinical Trial of Focal Traumatic Brain Injury","volume":"36","author":"Karlsson","year":"2019","journal-title":"J. Neurotrauma"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1007\/s13311-023-01414-z","article-title":"Cyclosporine as Therapy for Traumatic Brain Injury","volume":"20","author":"Hansson","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1017\/S0963180115000079","article-title":"The Flaws and Human Harms of Animal Experimentation","volume":"24","author":"Akhtar","year":"2015","journal-title":"Camb. Q. Healthc. Ethics"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Coyoy-Salgado, A., Segura-Uribe, J., Salgado-Ceballos, H., Castillo-Mendieta, T., S\u00e1nchez-Torres, S., Freyermuth-Trujillo, X., Orozco-Barrios, C., Orozco-Suarez, S., Feria-Romero, I., and Pinto-Almaz\u00e1n, R. (2024). Evaluating Sex Steroid Hormone Neuroprotection in Spinal Cord Injury in Animal Models: Is It Promising in the Clinic?. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071478"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1080\/00952990.2022.2114004","article-title":"Safety and Tolerability of Progesterone Treatment for Women with Cocaine Use Disorder: A Pilot Treatment Trial","volume":"48","author":"Oliva","year":"2022","journal-title":"Am. J. Drug Alcohol Abus."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.seizure.2023.05.004","article-title":"Progesterone and Its Derivatives for the Treatment of Catamenial Epilepsy: A Systematic Review","volume":"109","author":"Nucera","year":"2023","journal-title":"Seizure Eur. J. Epilepsy"},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Hernandez, G.D., and Brinton, R.D. (2022). Allopregnanolone: Regenerative Therapeutic to Restore Neurological Health. Neurobiol. Stress, 21.","DOI":"10.1016\/j.ynstr.2022.100502"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Sitruk-Ware, R., Sussman, H., Brinton, R., Schumacher, M., Singer, P., Kumar, N., De Nicola, A.F., El-Etr, M., Guennoun, R.V., and Borlongan, C. (2024). Nestorone (segesterone acetate) effects on neuroregeneration. Front. Neuroendocrinol., 73.","DOI":"10.1016\/j.yfrne.2024.101136"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.neubiorev.2020.12.007","article-title":"Progress in Progestin-Based Therapies for Neurological Disorders","volume":"122","author":"Bonsack","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s00213-005-0136-y","article-title":"Effects of DHEA Administration on Episodic Memory, Cortisol and Mood in Healthy Young Men: A Double-Blind, Placebo-Controlled Study","volume":"188","author":"Alhaj","year":"2006","journal-title":"Psychopharmacology"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1212\/01.WNL.0000052994.54660.58","article-title":"DHEA Treatment of Alzheimer\u2019s Disease: A Randomized, Double-Blind, Placebo-Controlled Study","volume":"60","author":"Wolkowitz","year":"2003","journal-title":"Neurology"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1081\/DDC-100107328","article-title":"Development of Patches for the Controlled Release of Dehydroepiandrosterone","volume":"27","author":"Minghetti","year":"2001","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/s41467-021-20948-4","article-title":"Transdermal Electroosmotic Flow Generated by a Porous Microneedle Array Patch","volume":"12","author":"Kusama","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Alex, M., Alsawaftah, N.M., and Husseini, G.A. (2024). State-of-All-the-Art and Prospective Hydrogel-Based Transdermal Drug Delivery Systems. Appl. Sci., 14.","DOI":"10.3390\/app14072926"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Siafaka, P.I., \u00d6zcan B\u00fclb\u00fcl, E., Okur, M.E., Karantas, I.D., and \u00dcst\u00fcnda\u011f Okur, N. (2023). The Application of Nanogels as Efficient Drug Delivery Platforms for Dermal\/Transdermal Delivery. Gels, 9.","DOI":"10.3390\/gels9090753"},{"key":"ref_188","doi-asserted-by":"crossref","unstructured":"Lunter, D., Klang, V., Eichner, A., Savic, S.M., Savic, S., Lian, G., and Erd\u0151, F. (2024). Progress in Topical and Transdermal Drug Delivery Research\u2014Focus on Nanoformulations. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16060817"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"178","DOI":"10.5534\/wjmh.190006","article-title":"Testosterone and Dehydroepiandrosterone Treatment in Ageing Men: Are We All Set?","volume":"38","author":"Walther","year":"2020","journal-title":"World J. Mens. Health"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/7\/945\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:57:00Z","timestamp":1760032620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/7\/945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,23]]},"references-count":189,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ph18070945"],"URL":"https:\/\/doi.org\/10.3390\/ph18070945","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,23]]}}}