{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T23:15:19Z","timestamp":1776122119263,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our previous studies have demonstrated that specific peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3) agonists play a fundamental role in oligodendrocyte progenitor (OP) differentiation, protecting them against oxidative and inflammatory damage. The antihypertensive drug Telmisartan (TLM) was shown to act as a PPAR-\u03b3 modulator. This study investigates the TLM effect on OP differentiation and validates its capability to restore damage in a pharmacological model of Niemann-Pick type C (NPC) disease through a PPAR-\u03b3-mediated mechanism. For the first time in purified OPs, we demonstrate that TLM-induced PPAR-\u03b3 activation downregulates the type 1 angiotensin II receptor (AT1), the level of which naturally decreases during differentiation. Like other PPAR-\u03b3 agonists, we show that TLM promotes peroxisomal proliferation and promotes OP differentiation. Furthermore, TLM can offset the OP maturation arrest induced by a lysosomal cholesterol transport inhibitor (U18666A), which reproduces an NPC1-like phenotype. In the NPC1 model, TLM also reduces cholesterol accumulation within peroxisomal and lysosomal compartments and the contacts between lysosomes and peroxisomes, revealing that TLM can regulate intracellular cholesterol transport, crucial for myelin formation. Altogether, these data indicate a new potential use of TLM in hypomyelination pathologies such as NPC1, underlining the possible repositioning of the drug already used in other pathologies.<\/jats:p>","DOI":"10.3390\/ijms22179434","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T22:49:51Z","timestamp":1630363791000},"page":"9434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Antihypertensive Drug Telmisartan Protects Oligodendrocytes from Cholesterol Accumulation and Promotes Differentiation by a PPAR-\u03b3-Mediated Mechanism"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6590-7530","authenticated-orcid":false,"given":"Antonietta","family":"Bernardo","sequence":"first","affiliation":[{"name":"National Center for Research and Preclinical and Clinical Evaluation of Drugs, Istituto Superiore di Sanit\u00e0, 00169 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-9685","authenticated-orcid":false,"given":"Mariagiovanna","family":"Malara","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-2376","authenticated-orcid":false,"given":"Lucia","family":"Bertuccini","sequence":"additional","affiliation":[{"name":"Core Facilities, Istituto Superiore di Sanit\u00e0, 00169 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"De Nuccio","sequence":"additional","affiliation":[{"name":"Research Coordination and Support Service, Istituto Superiore di Sanit\u00e0, 00169 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Visentin","sequence":"additional","affiliation":[{"name":"National Center for Research and Preclinical and Clinical Evaluation of Drugs, Istituto Superiore di Sanit\u00e0, 00169 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-4689","authenticated-orcid":false,"given":"Luisa","family":"Minghetti","sequence":"additional","affiliation":[{"name":"Research Coordination and Support Service, Istituto Superiore di Sanit\u00e0, 00169 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/ajh\/hpu197","article-title":"Neuroprotective Effects of Angiotensin Receptor Blockers","volume":"28","author":"Villapol","year":"2015","journal-title":"Am. J. Hypertens."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.2337\/diabetes.54.12.3442","article-title":"Molecular Characterization of New Selective Peroxisome Proliferator-Activated Receptor Modulators With Angiotensin Receptor Blocking Activity","volume":"54","author":"Schupp","year":"2005","journal-title":"Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1248\/bpb.b12-00387","article-title":"Ameliorative Effects of Telmisartan on the Inflammatory Response and Impaired Spatial Memory in a Rat Model of Alzheimer\u2019s Disease Incorporating Additional Cerebrovascular Disease Factors","volume":"35","author":"Shindo","year":"2012","journal-title":"Biol. Pharm. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kolli, V., Stechschulte, L.A., Dowling, A.R., Rahman, S., Czernik, P.J., and Lecka-Czernik, B. (2014). Partial Agonist, Telmisartan, Maintains PPAR\u03b3 Serine 112 Phosphorylation, and Does Not Affect Osteoblast Differentiation and Bone Mass. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096323"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.neuropharm.2013.11.022","article-title":"Telmisartan Ameliorates Glutamate-Induced Neurotoxicity: Roles of AT1 Receptor Blockade and PPAR\u03b3 Activation","volume":"79","author":"Wang","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.cardiores.2006.07.014","article-title":"Telmisartan Downregulates Angiotensin II Type 1 Receptor through Activation of Peroxisome Proliferator-Activated Receptor \u03b3","volume":"72","author":"Imayama","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jstrokecerebrovasdis.2017.01.025","article-title":"Effect of Telmisartan on Preventing Learning and Memory Deficits Via Peroxisome Proliferator-Activated Receptor-\u03b3 in Vascular Dementia Spontaneously Hypertensive Rats","volume":"27","author":"Gao","year":"2018","journal-title":"J. Stroke Cerebrovasc. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zhang, T., Li, C., Guo, J., Xu, B., and Xue, L. (2021). Telmisartan Attenuates Human Glioblastoma Cells Proliferation and Oncogenicity by Inducing the Lipid Oxidation. Asia-Pac. J. Clin. Oncol.","DOI":"10.1111\/ajco.13574"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2174\/138161206780574579","article-title":"PPAR-\u03b3; Agonists as Regulators of Microglial Activation and Brain Inflammation","volume":"12","author":"Bernardo","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/ncpneuro0586","article-title":"Drug Insight: Effects Mediated by Peroxisome Proliferator-Activated Receptor-\u03b3 in CNS Disorders","volume":"3","author":"Heneka","year":"2007","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fakan, B., Szalardy, L., and Vecsei, L. (2019). Exploiting the Therapeutic Potential of Endogenous Immunomodulatory Systems in Multiple Sclerosis\u2014Special Focus on the Peroxisome Proliferator-Activated Receptors (PPARs) and the Kynurenines. IJMS, 20.","DOI":"10.3390\/ijms20020426"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10571-017-0554-5","article-title":"Roles of Peroxisome Proliferator-Activated Receptor Gamma on Brain and Peripheral Inflammation","volume":"38","author":"Villapol","year":"2018","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejphar.2016.02.042","article-title":"Inhibition of Endoplasmic Reticulum Stress-Activated IRE1\u03b1-TRAF2-Caspase-12 Apoptotic Pathway Is Involved in the Neuroprotective Effects of Telmisartan in the Rotenone Rat Model of Parkinson\u2019s Disease","volume":"776","author":"Tong","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1139\/cjpp-2017-0042","article-title":"Protective Effects of Telmisartan and Tempol on Lipopolysaccharide-Induced Cognitive Impairment, Neuroinflammation, and Amyloidogenesis: Possible Role of Brain-Derived Neurotrophic Factor","volume":"95","author":"Khallaf","year":"2017","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111441","DOI":"10.1016\/j.fct.2020.111441","article-title":"The Anti-Alzheimer Effect of Telmisartan in a Hyperglycemic Ovariectomized Rat Model; Role of Central Angiotensin and Estrogen Receptors","volume":"142","author":"Khallaf","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Abd El Aziz, A.E., Sayed, R.H., Sallam, N.A., and El Sayed, N.S. (2021). Neuroprotective Effects of Telmisartan and Nifedipine Against Cuprizone-Induced Demyelination and Behavioral Dysfunction in Mice: Roles of NF-\u039aB and Nrf2. Inflammation.","DOI":"10.1007\/s10753-021-01447-6"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/aps.2013.199","article-title":"Telmisartan Protects Central Neurons against Nutrient Deprivation-Induced Apoptosis in Vitro through Activation of PPAR\u03b3 and the Akt\/GSK-3\u03b2 Pathway","volume":"35","author":"Pang","year":"2014","journal-title":"Acta Pharm. Sin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1007\/s12035-018-1300-9","article-title":"Telmisartan Protects a Microglia Cell Line from LPS Injury Beyond AT1 Receptor Blockade or PPAR\u03b3 Activation","volume":"56","author":"Elkahloun","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1515\/hsz-2013-0152","article-title":"The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-\u03b3 Promotes Oligodendrocyte Differentiation through Mechanisms Involving Mitochondria and Oscillatory Ca2+ Waves","volume":"394","author":"Bernardo","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1097\/NEN.0b013e3182309ab1","article-title":"Peroxisome Proliferator-Activated Receptor \u03b3 Agonists Accelerate Oligodendrocyte Maturation and Influence Mitochondrial Functions and Oscillatory Ca 2+ Waves","volume":"70","author":"Bernardo","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.expneurol.2015.07.014","article-title":"Peroxisome Proliferator Activated Receptor-\u03b3 Agonists Protect Oligodendrocyte Progenitors against Tumor Necrosis Factor-Alpha-Induced Damage: Effects on Mitochondrial Functions and Differentiation","volume":"271","author":"Bernardo","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.pathophys.2016.05.007","article-title":"Regulation of Oligodendrocyte Differentiation: Insights and Approaches for the Management of Neurodegenerative Disease","volume":"23","author":"Tauheed","year":"2016","journal-title":"Pathophysiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.12688\/f1000research.20904.1","article-title":"Epigenetic Regulation of Oligodendrocyte Myelination in Developmental Disorders and Neurodegenerative Diseases","volume":"9","author":"Berry","year":"2020","journal-title":"F1000Research"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/glia.1078","article-title":"Angiotensin Receptor-like Immunoreactivity in Adult Brain White Matter Astrocytes and Oligodendrocytes","volume":"35","author":"Fogarty","year":"2001","journal-title":"Glia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1097\/NEN.0b013e3181aba2c1","article-title":"Peroxisome Proliferator-Activated Receptor-\u03b3 Agonists Promote Differentiation and Antioxidant Defenses of Oligodendrocyte Progenitor Cells","volume":"68","author":"Bernardo","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/meth.2001.1203","article-title":"Analysis of Fractal Dimension of O2A Glial Cells Differentiating in Vitro","volume":"24","author":"Behar","year":"2001","journal-title":"Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1006\/meth.2001.1201","article-title":"Use of Fractal Theory in Neuroscience: Methods, Advantages, and Potential Problems","volume":"24","author":"Jelinek","year":"2001","journal-title":"Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nmeth.3125","article-title":"Neuronal Morphometry Directly from Bitmap Images","volume":"11","author":"Ferreira","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.brainresprot.2005.06.001","article-title":"Proliferation Markers in the Adult Rodent Brain: Bromodeoxyuridine and Proliferating Cell Nuclear Antigen","volume":"15","author":"Valero","year":"2005","journal-title":"Brain Res. Protoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s00221-010-2491-0","article-title":"Increased BrdU Incorporation Reflecting DNA Repair, Neuronal de-Differentiation or Possible Neurogenesis in the Adult Cochlear Nucleus Following Bilateral Cochlear Lesions in the Rat","volume":"210","author":"Zheng","year":"2011","journal-title":"Exp. Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/s11745-009-3305-7","article-title":"Cholesterol Synthesis Inhibitor U18666A and the Role of Sterol Metabolism and Trafficking in Numerous Pathophysiological Processes","volume":"44","author":"Cenedella","year":"2009","journal-title":"Lipids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9782","DOI":"10.1038\/s41598-019-46268-8","article-title":"Adenosine A2A Receptor Stimulation Restores Cell Functions and Differentiation in Niemann-Pick Type C-like Oligodendrocytes","volume":"9","author":"Bernardo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.cell.2015.02.019","article-title":"Cholesterol Transport through Lysosome-Peroxisome Membrane Contacts","volume":"161","author":"Chu","year":"2015","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1074\/jbc.272.10.6245","article-title":"Peroxisomal Impairment in Niemann-Pick Type C Disease","volume":"272","author":"Schedin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez, M.C., Balboa, E., Alvarez, A.R., and Zanlungo, S. (2012). Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease. Oxidative Med. Cell. Longev., 2012.","DOI":"10.1155\/2012\/205713"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10545-014-9794-4","article-title":"Complex Lipid Trafficking in Niemann-Pick Disease Type C","volume":"38","author":"Vanier","year":"2015","journal-title":"J. Inherit. Metab Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.brainres.2016.03.035","article-title":"Lysosome and Endoplasmic Reticulum Quality Control Pathways in Niemann-Pick Type C Disease","volume":"1649","author":"Schultz","year":"2016","journal-title":"Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"s9","DOI":"10.1007\/s00592-005-0176-0","article-title":"Treating the Metabolic Syndrome: Telmisartan as a Peroxisome Proliferator-Activated Receptor-Gamma Activator","volume":"42","author":"Kurtz","year":"2005","journal-title":"Acta Diabetol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1475-2840-4-6","article-title":"Metabolic Effect of Telmisartan and Losartan in Hypertensive Patients with Metabolic Syndrome","volume":"4","author":"Vitale","year":"2005","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1475-2840-11-139","article-title":"Telmisartan Ameliorates Insulin Sensitivity by Activating the AMPK\/SIRT1 Pathway in Skeletal Muscle of Obese Db\/Db Mice","volume":"11","author":"Shiota","year":"2012","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"113674","DOI":"10.1016\/j.bcp.2019.113674","article-title":"Telmisartan Ameliorates A\u03b2 Oligomer-Induced Inflammation via PPAR\u03b3\/PTEN Pathway in BV2 Microglial Cells","volume":"171","author":"Wang","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.2174\/1567202612666150104150310","article-title":"Telmisartan Promotes Potential Glucose Homeostasis in Stroke-Resistant Spontaneously Hypertensive Rats via Peroxisome Proliferator-Activated Receptor. \u03b3 Activation","volume":"12","author":"Omote","year":"2015","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/cmdc.200800285","article-title":"Characterization of New PPAR\u03b3 Agonists: Analysis of Telmisartan\u2019s Structural Components","volume":"4","author":"Goebel","year":"2009","journal-title":"ChemMedChem"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Bernardo, A., and Minghetti, L. (2008). Regulation of Glial Cell Functions by PPAR- Natural and Synthetic Agonists. PPAR Res., 2008.","DOI":"10.1155\/2008\/864140"},{"key":"ref_45","first-page":"746","article-title":"Dysregulation of Cholesterol Balance in the Brain: Contribution to Neurodegenerative Diseases","volume":"5","author":"Vance","year":"2012","journal-title":"Dis. Models Mech."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yu, T., and Lieberman, A.P. (2013). Npc1 Acting in Neurons and Glia Is Essential for the Formation and Maintenance of CNS Myelin. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003462"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/B978-0-12-386487-1.00017-1","article-title":"Analysis of Cholesterol Trafficking with Fluorescent Probes","volume":"Volume 108","author":"Maxfield","year":"2012","journal-title":"Methods in Cell Biology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s11011-019-00445-w","article-title":"Laboratory Diagnosis of the Niemann-Pick Type C Disease: An Inherited Neurodegenerative Disorder of Cholesterol Metabolism","volume":"34","author":"Sitarska","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Nunes, M.J., Moutinho, M., Gama, M.J., Rodrigues, C.M.P., and Rodrigues, E. (2013). Histone Deacetylase Inhibition Decreases Cholesterol Levels in Neuronal Cells by Modulating Key Genes in Cholesterol Synthesis, Uptake and Efflux. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053394"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2015.03.046","article-title":"Close Encounters of the Lysosome-Peroxisome Kind","volume":"161","author":"Jin","year":"2015","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s11427-019-9569-9","article-title":"Cholesterol Transport through the Peroxisome-ER Membrane Contacts Tethered by PI(4,5)P2 and Extended Synaptotagmins","volume":"62","author":"Xiao","year":"2019","journal-title":"Sci. China Life Sci."},{"key":"ref_52","first-page":"1013","article-title":"Docosahexaenoic Acid Promotes Oligodendrocyte Differentiation via PPAR-\u03b3 Signalling and Prevents Tumor Necrosis Factor-\u03b1-Dependent Maturational Arrest","volume":"1862","author":"Bernardo","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Mol. Cell Biol. Lipids"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4952","DOI":"10.1038\/s41598-021-83938-y","article-title":"Curcumin Promotes Oligodendrocyte Differentiation and Their Protection against TNF-\u03b1 through the Activation of the Nuclear Receptor PPAR-\u03b3","volume":"11","author":"Bernardo","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kaitsuka, T., and Hakim, F. (2021). Response of Pluripotent Stem Cells to Environmental Stress and Its Application for Directed Differentiation. Biology, 10.","DOI":"10.3390\/biology10020084"},{"key":"ref_55","first-page":"1086","article-title":"SH-SY5Y Human Neuroblastoma Cell Line: In Vitro Cell Model of Dopaminergic Neurons in Parkinson\u2019s Disease","volume":"123","author":"Xie","year":"2010","journal-title":"Chin. Med. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/cyto.a.20896","article-title":"Quantifying Colocalization by Correlation: The Pearson Correlation Coefficient Is Superior to the Mander\u2019s Overlap Coefficient","volume":"77A","author":"Adler","year":"2010","journal-title":"Cytometry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1460-9568.2010.07283.x","article-title":"Serotonin Receptor 1A Modulates Actin Dynamics and Restricts Dendritic Growth in Hippocampal Neurons: Htr1a and Dendritic Growth","volume":"32","author":"Ferreira","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Zhang, F., Lavan, B.E., and Gregoire, F.M. (2007). Selective Modulators of PPAR-\u03b3 Activity: Molecular Aspects Related to Obesity and Side-Effects. PPAR Res., 2007.","DOI":"10.1155\/2007\/32696"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"113535","DOI":"10.1016\/j.ejmech.2021.113535","article-title":"Natural Products and Analogs as Preventive Agents for Metabolic Syndrome via Peroxisome Proliferator-Activated Receptors: An Overview","volume":"221","author":"Ferri","year":"2021","journal-title":"Eur. J. Med. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9434\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:52:51Z","timestamp":1760165571000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/17\/9434"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":59,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22179434"],"URL":"https:\/\/doi.org\/10.3390\/ijms22179434","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,30]]}}}