{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:14:21Z","timestamp":1764080061251,"version":"build-2065373602"},"reference-count":178,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC2024-2025 (FSG)"],"award-info":[{"award-number":["RC2024-2025 (FSG)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Neuromodulatory subcortical systems (NSSs) are monoaminergic and cholinergic neuronal groups that are markedly and precociously involved in the pathogenesis of many neurodegenerative disorders (NDDs), including Parkinson\u2019s and Alzheimer\u2019s diseases. In humans, although many tools have been developed to infer information on these nuclei, encompassing neuroimaging and neurophysiological methods, a detailed and specific direct evaluation of their cellular features in vivo has been difficult to obtain until recent years. The development of induced pluripotent stem cell (iPSC) models has allowed research to deeply delve into the cellular and molecular biology of NSS neurons. In fact, iPSCs can be produced easily and non-invasively from patients\u2019 fibroblasts or circulating blood monocytes, by de-differentiating those cells using specific protocols, and then be re-differentiated towards neural phenotypes, which may reproduce the specific features of the correspondent brain neurons (including NSS ones) from the same patient. In this review, we summarized findings obtained in the field of NDDs using iPSCs, with the aim to understand how reliably these might represent in vitro models of NSS. We found that most of the current literature in the field of iPSCs and NSSs in NDDs has focused on midbrain dopaminergic neurons in Parkinson\u2019s disease, providing interesting results on cellular pathophysiology and even leading to the first human autologous transplantation. Differentiation protocols for noradrenergic, cholinergic, and serotoninergic neurons have also been recently defined and published. Thus, it might be expected that in the near future, this approach could extend to other NSSs and other NDDs.<\/jats:p>","DOI":"10.3390\/cimb46090607","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T09:23:04Z","timestamp":1726737784000},"page":"10180-10199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1894-4128","authenticated-orcid":false,"given":"Alessandro","family":"Galgani","sequence":"first","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Scotto","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"},{"name":"Istituto Italiano di Tecnologia, 16163 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2940-8128","authenticated-orcid":false,"given":"Filippo S.","family":"Giorgi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy"},{"name":"IRCCS Stella Maris Foundation, 56128 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref_1","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"John Wiley & Sons, Ltd (2023). 2023 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 19, 1598\u20131695.","DOI":"10.1002\/alz.13016"},{"key":"ref_3","first-page":"21","article-title":"Priorities for research on neuromodulatory subcortical systems in Alzheimer\u2019s disease: Position paper from the NSS PIA of ISTAART","volume":"8","author":"Ehrenberg","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_4","unstructured":"Paxinos, G., and Mai, J.K. (2003). The Human Nervous System, Elsevier Inc.. [2nd ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1016\/S0140-6736(09)60492-X","article-title":"Parkinson\u2019s disease","volume":"373","author":"Lees","year":"2009","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1002\/cne.23415","article-title":"Cholinergic circuitry of the human nucleus basalis and its fate in Alzheimer\u2019s disease","volume":"521","author":"Mesulam","year":"2013","journal-title":"J. Comp. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jalz.2016.06.2362","article-title":"Locus coeruleus volume and cell population changes during Alzheimer\u2019s disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery","volume":"13","author":"Theofilas","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40478-017-0411-2","article-title":"Locus coeruleus cellular and molecular pathology during the progression of Alzheimer\u2019s disease","volume":"5","author":"Kelly","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s11910-023-01324-9","article-title":"Exploring the Role of Locus Coeruleus in Alzheimer\u2019s Disease: A Comprehensive Update on MRI Studies and Implications","volume":"23","author":"Galgani","year":"2023","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Giorgi, F.S., Ryskalin, L., Ruffoli, R., Biagioni, F., Limanaqi, F., Ferrucci, M., Busceti, C.L., Bonuccelli, U., and Fornai, F. (2017). The Neuroanatomy of the Reticular Nucleus Locus Coeruleus in Alzheimer\u2019s Disease. Front. Neuroanat., 11.","DOI":"10.3389\/fnana.2017.00080"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00702-021-02338-8","article-title":"The connections of Locus Coeruleus with hypothalamus: Potential involvement in Alzheimer\u2019s disease","volume":"128","author":"Giorgi","year":"2021","journal-title":"J. Neural Transm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/jnen\/nlx113","article-title":"Selective Vulnerability of Brainstem Nuclei in Distinct Tauopathies: A Postmortem Study","volume":"77","author":"Eser","year":"2018","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.jalz.2019.06.3916","article-title":"Profound degeneration of wake-promoting neurons in Alzheimer\u2019s disease","volume":"15","author":"Oh","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/mdc3.12590","article-title":"Nigrosome Imaging and Neuromelanin Sensitive MRI in Diagnostic Evaluation of Parkinsonism","volume":"5","author":"Pavese","year":"2018","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11910-020-01087-7","article-title":"Locus Coeruleus Magnetic Resonance Imaging in Neurological Diseases","volume":"21","author":"Galgani","year":"2020","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Vadodaria, K.C., Jones, J.R., Linker, S., and Gage, F.H. (2020). Modeling Brain Disorders Using Induced Pluripotent Stem Cells. Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a035659"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-62703-348-0_3","article-title":"A Review of the Methods for Human iPSC Derivation","volume":"997","author":"Malik","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Beghini, D.G., Kasai-Brunswick, T.H., and Henriques-Pons, A. (2024). Induced Pluripotent Stem Cells in Drug Discovery and Neurodegenerative Disease Modelling. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042392"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13024-016-0106-3","article-title":"Induced pluripotent stem cells in Alzheimer\u2019s disease: Applications for disease modeling and cell-replacement therapy","volume":"11","author":"Yang","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/cpr.12229","article-title":"Induced pluripotent stem cells and Parkinson\u2019s disease: Modelling and treatment","volume":"49","author":"Xu","year":"2016","journal-title":"Cell Prolif."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00109-017-1533-5","article-title":"Induced pluripotent stem cell-based modeling of neurodegenerative diseases: A focus on autophagy","volume":"95","author":"Jungverdorben","year":"2017","journal-title":"J. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"768391","DOI":"10.1155\/2014\/768391","article-title":"A Comparative View on Human Somatic Cell Sources for iPSC Generation","volume":"2014","author":"Raab","year":"2014","journal-title":"Stem Cells Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3233\/JAD-142682","article-title":"Turning on the Light Within: Subcortical Nuclei of the Isodentritic Core and their Role in Alzheimer\u2019s Disease Pathogenesis","volume":"46","author":"Theofilas","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"ref_25","unstructured":"Fornai, F., and Lenzi, P. (2020). Sistema Nervoso Vegetativo: Anatomia Funzionale Della Vita Vegetativa, Pisa University Press. [1st ed.]."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/0013-4694(49)90219-9","article-title":"Brain stem reticular formation and activation of the EEG","volume":"1","author":"Moruzzi","year":"1949","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0079-6123(03)45004-8","article-title":"The cholinergic innervation of the human cerebral cortex","volume":"145","author":"Mesulam","year":"2004","journal-title":"Prog. Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/BF02147990","article-title":"Localization of monoamines in the lower brain stem","volume":"20","author":"Fuxe","year":"1964","journal-title":"Experientia"},{"key":"ref_29","first-page":"1","article-title":"Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons","volume":"62","author":"Dahlstrom","year":"1964","journal-title":"Acta Physiol. Scand. Suppl."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/cne.902750205","article-title":"Nucleus basalis (Ch4) and cortical cholinergic innervation in the human brain: Observations based on the distribution of acetylcholinesterase and choline acetyltransferase","volume":"275","author":"Mesulam","year":"1988","journal-title":"J. Comp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jchemneu.2003.10.002","article-title":"The human raphe nuclei and the serotonergic system","volume":"26","author":"Hornung","year":"2003","journal-title":"J. Chem. Neuroanat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jchemneu.2011.05.011","article-title":"Collateralized dorsal raphe nucleus projections: A mechanism for the integration of diverse functions during stress","volume":"41","author":"Waselus","year":"2011","journal-title":"J. Chem. Neuroanat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"s130","DOI":"10.1007\/s10072-006-0587-x","article-title":"Pain-autonomic interactions","volume":"27","author":"Benarroch","year":"2006","journal-title":"Neurol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.smrv.2009.11.004","article-title":"The structure of the dorsal raphe nucleus and its relevance to the regulation of sleep and wakefulness","volume":"14","author":"Monti","year":"2010","journal-title":"Sleep. Med. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.pneurobio.2016.04.001","article-title":"Monoaminergic neuropathology in Alzheimer\u2019s disease","volume":"151","author":"Leko","year":"2017","journal-title":"Prog. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41583-020-0360-9","article-title":"Locus coeruleus: A new look at the blue spot","volume":"21","author":"Poe","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_37","unstructured":"Mai, J.K., and Paxinos, G. (2012). Locus Coeruleus. The Human Nervous System, Academic press. [3rd ed.]."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.brainres.2016.03.001","article-title":"Locus coeruleus: From global projection system to adaptive regulation of behavior","volume":"1645","author":"Waterhouse","year":"2016","journal-title":"Brain Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/sleep\/29.10.1327","article-title":"Circadian Regulation of Arousal: Role of the Noradrenergic Locus Coeruleus System and Light Exposure","volume":"29","year":"2006","journal-title":"Sleep"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.brainresbull.2019.08.007","article-title":"The role of Locus Coeruleus in neuroinflammation occurring in Alzheimer\u2019s disease","volume":"153","author":"Giorgi","year":"2019","journal-title":"Brain Res. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/jnc.13447","article-title":"Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: Noradrenergic signaling system","volume":"139","author":"Feinstein","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5410","DOI":"10.1523\/JNEUROSCI.0949-04.2004","article-title":"Locus ceruleus control of state-dependent gene expression","volume":"24","author":"Cirelli","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1126\/science.274.5290.1211","article-title":"Neuronal gene expression in the waking state: A role for the locus coeruleus","volume":"274","author":"Cirelli","year":"1996","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1097\/NEN.0b013e318232a379","article-title":"Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years","volume":"70","author":"Braak","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0149-7634(00)00028-2","article-title":"The role of the locus coeruleus in the development of Parkinson\u2019s disease","volume":"24","author":"Gesi","year":"2000","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1073\/pnas.0909586107","article-title":"Locus ceruleus controls Alzheimer\u2019s disease pathology by modulating microglial functions through norepinephrine","volume":"107","author":"Heneka","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.neuint.2010.02.001","article-title":"Induced LC degeneration in APP\/PS1 transgenic mice accelerates early cerebral amyloidosis and cognitive deficits","volume":"57","author":"Kummer","year":"2010","journal-title":"Neurochem. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1523\/JNEUROSCI.4236-05.2006","article-title":"Locus Ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice","volume":"26","author":"Heneka","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3393","DOI":"10.1111\/j.1460-9568.2006.05223.x","article-title":"Degeneration of noradrenergic fibres from the locus coeruleus causes tight-junction disorganisation in the rat brain","volume":"24","author":"Kalinin","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nrn.2016.165","article-title":"Ventral tegmental area: Cellular heterogeneity, connectivity and behaviour","volume":"18","author":"Morales","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Becker-Krail, D.D., Walker, W.H., and Nelson, R.J. (2022). The Ventral Tegmental Area and Nucleus Accumbens as Circadian Oscillators: Implications for Drug Abuse and Substance Use Disorders. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.886704"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1111\/jnc.13779","article-title":"Ventral tegmental area subcircuits process rewarding and aversive experiences","volume":"139","author":"Bariselli","year":"2016","journal-title":"J. Neurochem."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Oliva, I., and Wanat, M.J. (2016). Ventral tegmental area afferents and drug-dependent behaviors. Front. Psychiatry, 7.","DOI":"10.3389\/fpsyt.2016.00030"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.phrs.2018.01.016","article-title":"The role of dopaminergic midbrain in Alzheimer\u2019s disease: Translating basic science into clinical practice","volume":"130","author":"Mercuri","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2021.08.009","article-title":"Dopamine in Parkinson\u2019s disease","volume":"522","author":"Latif","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0306-4522(98)00202-4","article-title":"Cholinergic neurons of the nucleus basalis of Meynert receive cholinergic, catecholaminergic and GABAergic synapses: An electron microscopic investigation in the monkey","volume":"88","author":"Smiley","year":"1999","journal-title":"Neuroscience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1126\/science.7046051","article-title":"The cholinergic hypothesis of geriatric memory dysfunction","volume":"217","author":"Bartus","year":"1982","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1111\/ejn.14089","article-title":"Cholinergic modulation of spatial learning, memory and navigation","volume":"48","author":"Solari","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/ejn.13949","article-title":"Cholinergic modulation of striatal microcircuits","volume":"49","author":"Abudukeyoumu","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s00415-014-7439-z","article-title":"Atrophy of the cholinergic basal forebrain in dementia with Lewy bodies and Alzheimer\u2019s disease dementia","volume":"261","author":"Grothe","year":"2014","journal-title":"J. Neurol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Carsana, E.V., Audano, M., Breviario, S., Pedretti, S., Aureli, M., Lunghi, G., and Mitro, N. (2022). Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092069"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/s41596-021-00673-4","article-title":"Spotting-based differentiation of functional dopaminergic progenitors from human pluripotent stem cells","volume":"17","author":"Kim","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Novosadova, E., Dolotov, O., Inozemtseva, L., Novosadova, L., Antonov, S., Shimchenko, D., Bezuglov, V., Vetchinova, A., Tarantul, V., and Grivennikov, I. (2022). Influence of N-Arachidonoyl Dopamine and N-Docosahex-aenoyl Dopamine on the Expression of Neurotrophic Factors in Neuronal Differentiated Cultures of Human Induced Pluripotent Stem Cells under Conditions of Oxidative Stress. Antioxidants, 11.","DOI":"10.3390\/antiox11010142"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s00702-021-02303-5","article-title":"Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly","volume":"128","author":"Jansch","year":"2021","journal-title":"J. Neural Transm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"102027","DOI":"10.1016\/j.scr.2020.102027","article-title":"Developmental deficits and early signs of neurodegeneration revealed by PD patient derived dopamine neurons","volume":"49","author":"Luo","year":"2020","journal-title":"Stem Cell Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1172\/JCI130767","article-title":"Human autologous iPSC-derived dopaminergic progenitors restore motor function in Parkinson\u2019s disease models","volume":"130","author":"Song","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-019-2133-9","article-title":"Homogenous generation of dopaminergic neurons from multiple hiPSC lines by transient expression of transcription factors","volume":"10","author":"Mahajani","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1007\/s12035-016-0376-3","article-title":"Role of Dopamine D2\/D3 Receptors in Development, Plasticity, and Neuroprotection in Human iPSC-Derived Midbrain Dopaminergic Neurons","volume":"55","author":"Bono","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.scr.2016.10.008","article-title":"Generation of an iPSC line from a patient with tyrosine hydroxylase (TH) deficiency: TH-1 iPS.C","volume":"17","author":"Blau","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e00491","DOI":"10.1002\/brb3.491","article-title":"Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics","volume":"6","author":"Sheng","year":"2016","journal-title":"Brain Behav."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nbt.3435","article-title":"Generation of serotonin neurons from human pluripotent stem cells","volume":"34","author":"Lu","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/mp.2015.161","article-title":"Generation of functional human serotonergic neurons from fibroblasts","volume":"21","author":"Vadodaria","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbagen.2014.09.025","article-title":"Microencapsulation of dopamine neurons derived from human induced pluripotent stem cells","volume":"1850","author":"Konagaya","year":"2015","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.celrep.2014.10.023","article-title":"IPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for parkinson\u2019s disease","volume":"9","author":"Woodard","year":"2014","journal-title":"Cell Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"888","DOI":"10.5966\/sctm.2013-0213","article-title":"Proneural Transcription Factor Atoh1 Drives Highly Efficient Differentiation of Human Pluripotent Stem Cells Into Dopaminergic Neurons","volume":"3","author":"Sagal","year":"2014","journal-title":"Stem Cells Transl. Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Hartfield, E.M., Yamasaki-Mann, M., Ribeiro Fernandes, H.J., Vowles, J., James, W.S., Cowley, S.A., and Wade-Martins, R. (2014). Physiological characterisation of human iPS-derived dopaminergic neurons. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087388"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"473","DOI":"10.5966\/sctm.2012-0133","article-title":"Rapid Generation of Functional Dopaminergic Neurons From Human Induced Pluripotent Stem Cells Through a Single-Step Procedure Using Cell Lineage Transcription Factors","volume":"2","author":"Theka","year":"2013","journal-title":"Stem Cells Transl. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/emmm.201200215","article-title":"Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson\u2019s disease","volume":"4","author":"Caig","year":"2012","journal-title":"EMBO Mol. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nature10284","article-title":"Direct generation of functional dopaminergic neurons from mouse and human fibroblasts","volume":"476","author":"Caiazzo","year":"2011","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.stem.2011.01.013","article-title":"LRRK2 mutant iPSC-derived da neurons demonstrate increased susceptibility to oxidative stress","volume":"8","author":"Nguyen","year":"2011","journal-title":"Cell Stem Cell."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.mcn.2010.06.017","article-title":"Differentiation of human ES and Parkinson\u2019s disease iPS cells into ventral midbrain dopaminergic neurons requires a high activity form of SHH, FGF8a and specific regionalization by retinoic acid","volume":"45","author":"Cooper","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1002\/stem.499","article-title":"Efficient generation of functional dopaminergic neurons from human induced pluripotent stem cells under defined conditions","volume":"28","author":"Swistowski","year":"2010","journal-title":"Stem Cells"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.cell.2009.02.013","article-title":"Parkinson\u2019s Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming Factors","volume":"136","author":"Soldner","year":"2009","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sagar, R., Zivko, C., Xydia, A., Weisman, D.C., Lyketsos, C.G., and Mahairaki, V. (2023). Generation and Characterization of a Human-Derived and Induced Pluripotent Stem Cell (iPSC) Line from an Alzheimer\u2019s Disease Patient with Neuropsychiatric Symptoms. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123313"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"102486","DOI":"10.1016\/j.xpro.2023.102486","article-title":"Optimized protocol for the generation of functional human induced-pluripotent-stem-cell-derived dopaminergic neurons","volume":"4","author":"Sheta","year":"2023","journal-title":"STAR Protoc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"102658","DOI":"10.1016\/j.scr.2022.102658","article-title":"Increased excitability of human iPSC-derived neurons in HTR2A variant-related sleep bruxism","volume":"59","author":"Sarkar","year":"2022","journal-title":"Stem Cell Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1038\/s41467-020-17165-w","article-title":"Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson\u2019s disease","volume":"11","author":"Doi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jpor.2016.11.003","article-title":"Generation of neural cells using iPSCs from sleep bruxism patients with 5-HT2A polymorphism","volume":"61","author":"Hoashi","year":"2017","journal-title":"J. Prosthodont. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.bbagen.2015.04.011","article-title":"Maturation of human iPS cell-derived dopamine neuron precursors in alginate-Ca2+ hydrogel","volume":"1850","author":"Komatsu","year":"2015","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1038\/s41380-022-01628-1","article-title":"Generation of human A9 dopaminergic pacemakers from induced pluripotent stem cells","volume":"27","author":"Li","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/scrt423","article-title":"Functional differentiation of midbrain neurons from human cord blood-derived induced pluripotent stem cells","volume":"5","author":"Stanslowsky","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1002\/stem.1152","article-title":"Specification of midbrain dopamine neurons from primate pluripotent stem cells","volume":"30","author":"Xi","year":"2012","journal-title":"Stem Cells"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/term.2021","article-title":"Current advances in the generation of human iPS cells: Implications in cell-based regenerative medicine","volume":"10","author":"Revilla","year":"2016","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"73","DOI":"10.2174\/1566523211313020002","article-title":"Technological Overview of iPS Induction from Human Adult Somatic Cells","volume":"13","author":"Bayart","year":"2013","journal-title":"Curr. Gene Ther."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Katolikova, N.V., Khudiakov, A.A., Shafranskaya, D.D., Prjibelski, A.D., Masharskiy, A.E., Mor, M.S., Golovkin, A.S., Zaytseva, A.K., Neganova, I.E., and Efimova, E.V. (2023). Modulation of Notch Signaling at Early Stages of Differentiation of Human Induced Pluripotent Stem Cells to Dopaminergic Neurons. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021429"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Cardo, L.F., Monz\u00f3n-Sandoval, J., Li, Z., Webber, C., and Li, M. (2023). Single-Cell Transcriptomics and In Vitro Lineage Tracing Reveals Differential Susceptibility of Human iPSC-Derived Midbrain Dopaminergic Neurons in a Cellular Model of Parkinson\u2019s Disease. Cells, 12.","DOI":"10.3390\/cells12242860"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1002\/jcb.24183","article-title":"Assessing iPSC reprogramming methods for their suitability in translational medicine","volume":"113","author":"Rao","year":"2012","journal-title":"J. Cell Biochem."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Tao, Y., Li, X., Dong, Q., Kong, L., Petersen, A.J., Yan, Y., Xu, K., Zima, S., Li, Y., and Schmidt, D.K. (2023). Generation of locus coeruleus norepinephrine neurons from human pluripotent stem cells. Nat. Biotechnol., 1\u201313.","DOI":"10.1038\/s41587-023-01977-4"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Diao, X., Wang, F., Becerra-Calixto, A., Soto, C., and Mukherjee, A. (2021). Induced pluripotent stem cell-derived dopaminergic neurons from familial parkinson\u2019s disease patients display \u03b1-synuclein pathology and abnormal mitochondrial morphology. Cells, 10.","DOI":"10.3390\/cells10092402"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1016\/j.stemcr.2021.06.006","article-title":"Generation of caudal-type serotonin neurons and hindbrain-fate organoids from hPSCs","volume":"16","author":"Valiulahi","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"102486","DOI":"10.1016\/j.scr.2021.102486","article-title":"Generation of striatal neurons from human induced pluripotent stem cells by controlling extrinsic signals with small molecules","volume":"55","author":"Amimoto","year":"2021","journal-title":"Stem Cell Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/sctm.20-0014","article-title":"Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo","volume":"10","author":"Hiller","year":"2021","journal-title":"Stem Cells Transl. Med."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sanz Mu\u00f1oz, S., Engel, M., Balez, R., Do-Ha, D., Castro Cabral-Da-Silva, M., Hern\u00e1ndez, D., Berg, T., Fifita, J.A., Grima, N., and Yang, S. (2020). A simple differentiation protocol for generation of induced pluripotent stem cell-derived basal forebrain-like cholinergic neurons for alzheimer\u2019s disease and frontotemporal dementia disease modeling. Cells, 9.","DOI":"10.20944\/preprints202008.0091.v1"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1097\/WNR.0000000000001131","article-title":"(2 R,6 R)-Hydroxynorketamine promotes dendrite outgrowth in human inducible pluripotent stem cell-derived neurons through AMPA receptor with timing and exposure compatible with ketamine infusion pharmacokinetics in humans","volume":"29","author":"Collo","year":"2018","journal-title":"Neuroreport"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Fedele, S., Collo, G., Behr, K., Bischofberger, J., M\u00fcller, S., Kunath, T., Christensen, K., G\u00fcndner, A.L., Graf, M., and Jagasia, R. (2017). Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-05633-1"},{"key":"ref_108","first-page":"395","article-title":"Survival of human induced pluripotent stem cell-derived midbrain dopaminergic neurons in the brain of a primate model of Parkinson\u2019s disease","volume":"1","author":"Kikuchi","year":"2011","journal-title":"J. Park. Dis."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10648","article-title":"Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson\u2019s disease","volume":"480","author":"Kriks","year":"2011","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1124\/mol.62.1.65","article-title":"SB-431542 Is a Potent and Specific Inhibitor of Transforming Growth Factor-Superfamily Type I Activin Receptor-Like Kinase (ALK) Receptors ALK4, ALK5, and ALK7","volume":"62","author":"Inman","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1016\/j.biocel.2010.07.018","article-title":"Dorsomorphin and LDN-193189 inhibit BMP-mediated Smad, p38 and Akt signalling in C2C12 cells","volume":"42","author":"Boergermann","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1172\/JCI45794","article-title":"Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease","volume":"121","author":"Rhee","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ydbio.2004.07.038","article-title":"Retinoic-acid-concentration-dependent acquisition of neural cell identity during in vitro differentiation of mouse embryonic stem cells","volume":"275","author":"Okada","year":"2004","journal-title":"Dev. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1371\/journal.pbio.0050325","article-title":"The foxa2 gene controls the birth and spontaneous degeneration of dopamine neurons in old age","volume":"5","author":"Kittappa","year":"2007","journal-title":"PLoS Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1016\/j.febslet.2015.10.020","article-title":"Cell fate determination, neuronal maintenance and disease state: The emerging role of transcription factors Lmx1a and Lmx1b","volume":"589","author":"Ang","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1039\/C5LC00180C","article-title":"Differentiation of neuroepithelial stem cells into functional dopaminergic neurons in 3D microfluidic cell culture","volume":"15","author":"Moreno","year":"2015","journal-title":"Lab. Chip."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Sibuea, S., Ho, J.K., Pouton, C.W., and Haynes, J.M. (2023). TGF\u03b23, dibutyryl cAMP and a notch inhibitor modulate phenotype late in stem cell-derived dopaminergic neuron maturation. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1111705"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0301-0082(97)00066-X","article-title":"Transforming growth factor-\u03b2s in neurodegenerative disease","volume":"54","author":"Flanders","year":"1998","journal-title":"Prog. Neurobiol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.nbd.2006.10.005","article-title":"GDNF applied to the MPTP-lesioned nigrostriatal system requires TGF-\u03b2 for its neuroprotective action","volume":"25","author":"Schober","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1016\/j.celrep.2016.11.068","article-title":"TGF-\u03b2 Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning","volume":"17","author":"Luo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2612","DOI":"10.1046\/j.1471-4159.1995.65062612.x","article-title":"Effects of Dibutyryl Cyclic AMP and Retinoic Acid on the Differentiation of Dopamine Neurons: Prevention of Cell Death by Dibutyryl Cyclic AMP","volume":"65","author":"Mena","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.stemcr.2017.08.017","article-title":"Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson\u2019s Disease","volume":"9","author":"Wulansari","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1006\/mcne.1999.0826","article-title":"Specification of the central noradrenergic phenotype by the homeobox gene Phox2b","volume":"15","author":"Pattyn","year":"2000","journal-title":"Mol. Cell Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0896-6273(00)81242-8","article-title":"Defects in Sensory and Autonomic Ganglia and Absence of Locus Coeruleus in Mice Deficient for the Homeobox Gene Phox2a","volume":"18","author":"Morin","year":"1997","journal-title":"Neuron"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.celrep.2016.09.062","article-title":"Generating Late-Onset Human iPSC-Based Disease Models by Inducing Neuronal Age-Related Phenotypes through Telomerase Manipulation","volume":"17","author":"Vera","year":"2016","journal-title":"Cell Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/stem.1854","article-title":"Parkin Mutations Reduce the Complexity of Neuronal Processes in iPSC-Derived Human Neurons","volume":"33","author":"Ren","year":"2015","journal-title":"Stem Cells"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stemcr.2017.06.005","article-title":"MAPT Genetic Variation and Neuronal Maturity Alter Isoform Expression Affecting Axonal Transport in iPSC-Derived Dopamine Neurons","volume":"9","author":"Beevers","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1093\/hmg\/ddz038","article-title":"Cellular \u03b1-synuclein pathology is associated with bioenergetic dysfunction in Parkinson\u2019s iPSC-derived dopamine neurons","volume":"28","author":"Zambon","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.stemcr.2016.01.013","article-title":"ER Stress and Autophagic Perturbations Lead to Elevated Extracellular \u03b1-Synuclein in GBA-N370S Parkinson\u2019s iPSC-Derived Dopamine Neurons","volume":"6","author":"Fernandes","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.stemcr.2020.07.013","article-title":"Defects in Mitochondrial Biogenesis Drive Mitochondrial Alterations in PARKIN-Deficient Human Dopamine Neurons","volume":"15","author":"Kumar","year":"2020","journal-title":"Stem Cell Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"7693","DOI":"10.1523\/JNEUROSCI.0628-16.2016","article-title":"Activation of \u03b2-Glucocerebrosidase Reduces Pathological \u03b1-Synuclein and Restores Lysosomal Function in Parkinson\u2019s Patient Midbrain Neurons","volume":"36","author":"Mazzulli","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.stem.2018.10.023","article-title":"Single-Cell Sequencing of iPSC-Dopamine Neurons Reconstructs Disease Progression and Identifies HDAC4 as a Regulator of Parkinson Cell Phenotypes","volume":"24","author":"Lang","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_133","first-page":"1","article-title":"Genomic, transcriptomic, and metabolomic profiles of hiPSC-derived dopamine neurons from clinically discordant brothers with identical PRKN deletions","volume":"8","author":"Cukier","year":"2022","journal-title":"Npj Park. Dis."},{"key":"ref_134","first-page":"1","article-title":"Mutations in LRRK2 impair NF-\u039aB pathway in iPSC-derived neurons","volume":"13","author":"Lang","year":"2016","journal-title":"J. Neuroinflam."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.stemcr.2020.12.011","article-title":"Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells","volume":"16","author":"Schmidt","year":"2021","journal-title":"Stem Cell Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.stem.2020.08.002","article-title":"Defects in mRNA Translation in LRRK2-Mutant hiPSC-Derived Dopaminergic Neurons Lead to Dysregulated Calcium Homeostasis","volume":"27","author":"Kim","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s12035-016-0303-7","article-title":"LRRK2 expression is deregulated in fibroblasts and neurons from parkinson patients with mutations in PINK1","volume":"55","author":"Azkona","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1093\/brain\/awz084","article-title":"Cell-specific overexpression of COMT in dopaminergic neurons of Parkinson\u2019s disease","volume":"142","author":"Kuzumaki","year":"2019","journal-title":"Brain"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3522","DOI":"10.1007\/s12035-023-03293-z","article-title":"Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson\u2019s Disease Shifts the Transcriptome Towards the Normal State","volume":"60","author":"Lebedeva","year":"2023","journal-title":"Mol. Neurobiol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep34341","article-title":"Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele","volume":"6","author":"Oni","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Collo, G., Cavalleri, L., Zoli, M., Maskos, U., Ratti, E., and Pich, E.M. (2018). Alph\u03b16-containing nicotinic acetylcholine receptors mediate nicotine-induced structural plasticity in mouse and human iPSC-derived dopaminergic neurons. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00572"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2019.04.017","article-title":"Nicotine prevents alpha-synuclein accumulation in mouse and human iPSC-derived dopaminergic neurons through activation of the dopamine D3- acetylcholine nicotinic receptor heteromer","volume":"129","author":"Bono","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1007\/s12035-022-02748-z","article-title":"Structural Plasticity of Dopaminergic Neurons Requires the Activation of the D3R-nAChR Heteromer and the PI3K-ERK1\/2\/Akt-Induced Expression of c-Fos and p70S6K Signaling Pathway","volume":"59","author":"Mutti","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.neurobiolaging.2020.12.001","article-title":"Impaired dopamine D3 and nicotinic acetylcholine receptor membrane localization in iPSCs-derived dopaminergic neurons from two Parkinson\u2019s disease patients carrying the LRRK2 G2019S mutation","volume":"99","author":"Bono","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s42003-021-02973-7","article-title":"Single-cell transcriptomics of human iPSC differentiation dynamics reveal a core molecular network of Parkinson\u2019s disease","volume":"5","author":"Novak","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/mds.28786","article-title":"Molecular Features of Parkinson\u2019s Disease in Patient-Derived Midbrain Dopaminergic Neurons","volume":"37","author":"Ren","year":"2022","journal-title":"Mov. Disord."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/s41380-019-0377-5","article-title":"Altered serotonergic circuitry in SSRI-resistant major depressive disorder patient-derived neurons","volume":"24","author":"Vadodaria","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/s41380-019-0363-y","article-title":"Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons","volume":"24","author":"Vadodaria","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2174\/1874609812666190204094233","article-title":"Detecting Non-cognitive Features of Prodromal Neurodegenerative Diseases","volume":"11","author":"Seifan","year":"2019","journal-title":"Curr. Aging Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/toxsci\/kfx145","article-title":"From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons","volume":"159","author":"Neely","year":"2017","journal-title":"Toxicol. Sci."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Pamies, D., Wiersma, D., Katt, M.E., Zhao, L., Burtscher, J., Harris, G., Smirnova, L., Searson, P.C., Hartung, T., and Hogberg, H.T. (2022). Human IPSC 3D brain model as a tool to study chemical-induced dopaminergic neuronal toxicity. Neurobiol. Dis., 169.","DOI":"10.1016\/j.nbd.2022.105719"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1038\/mp.2017.241","article-title":"Ketamine enhances structural plasticity in mouse mesencephalic and human iPSC-derived dopaminergic neurons via AMPAR-driven BDNF and mTOR signaling","volume":"23","author":"Cavalleri","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2470547019842545","DOI":"10.1177\/2470547019842545","article-title":"Structural Plasticity Induced by Ketamine in Human Dopaminergic Neurons as Mechanism Relevant for Treatment-Resistant Depression","volume":"3","author":"Collo","year":"2019","journal-title":"Chronic Stress"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41591-019-0739-1","article-title":"iPSC modeling of young-onset Parkinson\u2019s disease reveals a molecular signature of disease and novel therapeutic candidates","volume":"26","author":"Laperle","year":"2020","journal-title":"Nat. Med."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Orlando, R., Ginerete, R.P., Cavalleri, L., Aliperti, V., Imbriglio, T., Battaglia, G., Zuena, A.R., Nicoletti, F., Merlo Pich, E., and Collo, G. (2022). Synergic action of L-acetylcarnitine and L-methylfolate in Mouse Models of Stress-Related Disorders and Human iPSC-Derived Dopaminergic Neurons. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.913210"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"108263","DOI":"10.1016\/j.celrep.2020.108263","article-title":"Single-Cell Transcriptomics of Parkinson\u2019s Disease Human In Vitro Models Reveals Dopamine Neuron-Specific Stress Responses","volume":"33","author":"Fernandes","year":"2020","journal-title":"Cell Rep."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1248\/bpb.b22-00839","article-title":"CRISPR-Cas9-Edited SNCA Knockout Human Induced Pluripotent Stem Cell-Derived Dopaminergic Neurons and Their Vulnerability to Neurotoxicity","volume":"46","author":"Inoue","year":"2023","journal-title":"Biol. Pharm. Bull."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13041-018-0349-8","article-title":"Down-regulation of ghrelin receptors on dopaminergic neurons in the substantia nigra contributes to Parkinson\u2019s disease-like motor dysfunction","volume":"11","author":"Suda","year":"2018","journal-title":"Mol. Brain"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.stemcr.2018.11.021","article-title":"Neurite Collapse and Altered ER Ca2+ Control in Human Parkinson Disease Patient iPSC-Derived Neurons with LRRK2 G2019S Mutation","volume":"12","author":"Korecka","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/mds.26082","article-title":"Levodopa therapy for Parkinson\u2019s disease: Pharmacokinetics and pharmacodynamics","volume":"30","author":"Lewitt","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"4995","DOI":"10.1523\/JNEUROSCI.2431-21.2022","article-title":"Understanding the Influence of Target Acquisition on Survival, Integration, and Phenotypic Maturation of Dopamine Neurons within Stem Cell-Derived Neural Grafts in a Parkinson\u2019s Disease Model","volume":"42","author":"Moriarty","year":"2022","journal-title":"J. Neurosci."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e24234","DOI":"10.1016\/j.heliyon.2024.e24234","article-title":"A cell therapy approach based on iPSC-derived midbrain organoids for the restoration of motor function in a Parkinson\u2019s disease mouse model","volume":"10","author":"Fu","year":"2024","journal-title":"Heliyon"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/978-1-0716-0655-1_3","article-title":"Engraftable Induced Pluripotent Stem Cell -Derived Neural Precursors for Brain Repair","volume":"2155","author":"Zygogianni","year":"2020","journal-title":"Methods Mol. Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1089\/scd.2023.0043","article-title":"Neurite Outgrowth and Gene Expression Profile Correlate with Efficacy of Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts","volume":"32","author":"Hills","year":"2023","journal-title":"Stem Cells Dev."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"114219","DOI":"10.1016\/j.expneurol.2022.114219","article-title":"Identifying the optimal developmental age of human pluripotent stem cell-derived midbrain dopaminergic progenitors for transplantation in a rodent model of Parkinson\u2019s disease","volume":"358","author":"Pavan","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_166","first-page":"515","article-title":"Grafts Derived from an \u03b1-Synuclein Triplication Patient Mediate Functional Recovery but Develop Disease-Associated Pathology in the 6-OHDA Model of Parkinson\u2019s Disease","volume":"11","author":"Shrigley","year":"2021","journal-title":"J. Park. Dis."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41536-022-00221-y","article-title":"Optimizing maturity and dose of iPSC-derived dopamine progenitor cell therapy for Parkinson\u2019s disease","volume":"7","author":"Hiller","year":"2022","journal-title":"Npj Regen. Med."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1056\/NEJMoa1915872","article-title":"Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson\u2019s Disease","volume":"382","author":"Schweitzer","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.scr.2016.08.013","article-title":"Advantages of nonhuman primates as preclinical models for evaluating stem cell-based therapies for Parkinson\u2019s disease","volume":"17","author":"Grow","year":"2016","journal-title":"Stem Cell Res."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tins.2018.01.010","article-title":"Long road to ruin: Noradrenergic dysfunction in neurodegenerative disease","volume":"41","author":"Weinshenker","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/jnen\/nlab017","article-title":"Pontine Arteriolosclerosis and Locus Coeruleus Oxidative Stress Differentiate Resilience from Mild Cognitive Impairment in a Clinical Pathologic Cohort","volume":"80","author":"Kelly","year":"2021","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00401-021-02315-1","article-title":"ApoE4 inhibition of VMAT2 in the locus coeruleus exacerbates Tau pathology in Alzheimer\u2019s disease","volume":"142","author":"Kang","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/s41594-022-00745-3","article-title":"Tau modification by the norepinephrine metabolite DOPEGAL stimulates its pathology and propagation","volume":"29","author":"Kang","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1172\/JCI130513","article-title":"Norepinephrine metabolite DOPEGAL activates AEP and pathological Tau aggregation in locus coeruleus","volume":"130","author":"Kang","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Capucciati, A., Zucca, F.A., Monzani, E., Zecca, L., Casella, L., and Hofer, T. (2021). Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models. Antioxidants, 10.","DOI":"10.3390\/antiox10060824"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00702-006-0453-2","article-title":"Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: Consequences for neuronal vulnerability","volume":"113","author":"Zucca","year":"2006","journal-title":"J. Neural Transm."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1006\/nbdi.2000.0289","article-title":"The single intranigral injection of LPS as a new model for studying the selective effects of inflammatory reactions on dopaminergic system","volume":"7","author":"Herrera","year":"2000","journal-title":"Neurobiol. Dis."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.bbi.2019.06.034","article-title":"Noradrenergic dysfunction accelerates LPS-elicited inflammation-related ascending sequential neurodegeneration and deficits in non-motor\/motor functions","volume":"81","author":"Song","year":"2019","journal-title":"Brain Behav. Immun."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/9\/607\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:56:37Z","timestamp":1760111797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/46\/9\/607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,14]]},"references-count":178,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["cimb46090607"],"URL":"https:\/\/doi.org\/10.3390\/cimb46090607","relation":{},"ISSN":["1467-3045"],"issn-type":[{"type":"electronic","value":"1467-3045"}],"subject":[],"published":{"date-parts":[[2024,9,14]]}}}