{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:12:53Z","timestamp":1790003573727,"version":"4.0.1"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":1749,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein \u03b1-synuclein (\u03b1-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of \u03b1-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB. However, examination of clinically relevant human NSCs in these models is hindered by the challenges of xenotransplantation and the confounding effects of immunosuppressant drugs on pathology and behavior. To address this challenge, we developed an immune-deficient transgenic model of DLB that lacks T-, B-, and NK-cells, yet exhibits progressive accumulation of human \u03b1-syn (h-\u03b1-syn)-laden inclusions and cognitive and motor impairments. We demonstrate that clinically relevant human neural progenitor cells (line CNS10-hNPCs) survive, migrate extensively and begin to differentiate preferentially into astrocytes following striatal transplantation into this DLB model. Critically, grafted CNS10-hNPCs rescue both cognitive and motor deficits after 1 and 3 months and, furthermore, restore striatal dopamine and glutamate systems. These behavioral and neurochemical benefits are likely achieved by reducing \u03b1-syn oligomers. Collectively, these results using a new model of DLB demonstrate that hNPC transplantation can impact a broad array of disease mechanisms and phenotypes and suggest a cellular therapeutic strategy that should be pursued.<\/jats:p>","DOI":"10.1002\/sctm.16-0362","type":"journal-article","created":{"date-parts":[[2017,2,22]],"date-time":"2017-02-22T10:06:42Z","timestamp":1487758002000},"page":"1477-1490","source":"Crossref","is-referenced-by-count":22,"title":["Human Neural Progenitor Transplantation Rescues Behavior and Reduces \u03b1-Synuclein in a Transgenic Model of Dementia with Lewy Bodies"],"prefix":"10.1093","volume":"6","author":[{"given":"Natalie R.S.","family":"Goldberg","sequence":"first","affiliation":[{"name":"a Department of Neurobiology and Behavior, Irvine, California, USA"},{"name":"b Sue and Bill Gross Stem Cell Research Center, Irvine, California, USA"},{"name":"c Institute for Memory Impairments and Neurological Disorders, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel E.","family":"Marsh","sequence":"additional","affiliation":[{"name":"a Department of Neurobiology and Behavior, Irvine, California, USA"},{"name":"b Sue and Bill Gross Stem Cell Research Center, Irvine, California, USA"},{"name":"c Institute for Memory Impairments and Neurological Disorders, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ochaba","sequence":"additional","affiliation":[{"name":"a Department of Neurobiology and Behavior, Irvine, California, USA"},{"name":"c Institute for Memory Impairments and Neurological Disorders, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon C.","family":"Shelley","sequence":"additional","affiliation":[{"name":"d Department of Biomedical Sciences, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayk","family":"Davtyan","sequence":"additional","affiliation":[{"name":"e Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"a Department of Neurobiology and Behavior, Irvine, California, USA"},{"name":"b Sue and Bill Gross Stem Cell Research Center, Irvine, California, USA"},{"name":"c Institute for Memory Impairments and Neurological Disorders, Irvine, California, USA"},{"name":"f Department of Psychiatry and Human Behavior, University of California, Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan S.","family":"Steffan","sequence":"additional","affiliation":[{"name":"f Department of Psychiatry and Human Behavior, University of California, Irvine, California, 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