{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:02:33Z","timestamp":1789786953748,"version":"4.0.1"},"reference-count":67,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82303549"],"award-info":[{"award-number":["82303549"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32200726"],"award-info":[{"award-number":["32200726"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative disorders are increasingly linked to a progressive decline in lysosomal function. Activating Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, has therefore emerged as a promising therapeutic strategy to enhance cellular clearance in these conditions. In this study, we identified KHS-101 as a novel TFEB activator through a high-throughput screen of blood\u2013brain-barrier-permeable small molecules. We demonstrated that KHS-101 promotes TFEB nuclear translocation, enhances lysosomal biogenesis and proteolytic activity, and increases autophagic flux. Furthermore, KHS-101 significantly accelerates the degradation of pathogenic A53T mutant \u03b1-synuclein in a cellular model of Parkinson\u2019s disease, suggesting its potential to mitigate \u03b1-synuclein-mediated proteotoxicity and hold neuroprotective potential. Our findings identify KHS-101 as a potent TFEB activator and highlight the therapeutic potential of modulating the autophagy-lysosomal pathway for treating Parkinson\u2019s disease and related disorders.<\/jats:p>","DOI":"10.3390\/ijms27020905","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:28:12Z","timestamp":1768555692000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of KHS-101 as a Transcription Factor EB Activator to Promote \u03b1-Synuclein Degradation"],"prefix":"10.3390","volume":"27","author":[{"given":"Haizhen","family":"Zhu","sequence":"first","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Ren","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6222-2053","authenticated-orcid":false,"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Li","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-2261","authenticated-orcid":false,"given":"Xin","family":"Pan","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0930-7924","authenticated-orcid":false,"given":"Jiayi","family":"Chen","sequence":"additional","affiliation":[{"name":"Nanhu Laboratory, State Key Laboratory of Biomedical Analysis (SKLBA, Formerly Known as National Center of Biomedical Analysis, NCBA), Beijing 100039, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41580-019-0185-4","article-title":"Lysosomes as Dynamic Regulators of Cell and Organismal Homeostasis","volume":"21","author":"Ballabio","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev-physiol-021014-071649","article-title":"Lysosomal Physiology","volume":"77","author":"Xu","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41556-018-0244-7","article-title":"The Lysosome as a Cellular Centre for Signalling, Metabolism and Quali Ty Control","volume":"21","author":"Lawrence","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.bbamcr.2008.07.014","article-title":"Autophagy: A Lysosomal Degradation Pathway with a Central Role in Health and Disease","volume":"1793","author":"Eskelinen","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7883","DOI":"10.1073\/pnas.112632299","article-title":"Neuronal Loss and Brain Atrophy in Mice Lacking Cathepsins B and L","volume":"99","author":"Felbor","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","first-page":"31","article-title":"Lipofuscin-like Substances Accumulate Rapidly in Brain, Retina and Internal Organs with Cysteine Protease Inhibition","volume":"266","author":"Ivy","year":"1989","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1038\/nm.3232","article-title":"The Role of Autophagy in Neurodegenerative Disease","volume":"19","author":"Nixon","year":"2013","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6926","DOI":"10.1523\/JNEUROSCI.0800-08.2008","article-title":"Autophagy Induction and Autophagosome Clearance in Neurons: Relationship to Autophagic Pathology in Alzheimer\u2019s Disease","volume":"28","author":"Boland","year":"2008","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1016\/j.autrev.2017.05.015","article-title":"Autophagy in Neuroinflammatory Diseases","volume":"16","author":"Muller","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/abbs\/gmp031","article-title":"The Lysosome and Neurodegenerative Diseases","volume":"41","author":"Zhang","year":"2009","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.arr.2016.05.004","article-title":"Disorders of Lysosomal Acidification\u2014The Emerging Role of v-ATPase in Aging and Neurodegenerative Disease","volume":"32","author":"Colacurcio","year":"2016","journal-title":"Ageing Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.neuron.2017.01.022","article-title":"Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities","volume":"93","author":"Menzies","year":"2017","journal-title":"Neuron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-med-050715-104432","article-title":"Lysosomal Proteins as a Therapeutic Target in Neurodegeneration","volume":"68","author":"Krainc","year":"2017","journal-title":"Annu. Rev. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"987","DOI":"10.4161\/auto.20256","article-title":"Lysosomal Dysfunction in Neurodegeneration: The Role of ATP13A2\/PARK9","volume":"8","author":"Usenovic","year":"2012","journal-title":"Autophagy"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.ejmech.2016.07.054","article-title":"Protein Aggregation and Neurodegenerative Diseases: From Theory to Therapy","volume":"124","author":"Kumar","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","first-page":"1","article-title":"Protein Aggregation and Degradation Mechanisms in Neurodegenerative Diseases","volume":"2","author":"Takalo","year":"2013","journal-title":"Am. J. Neurodegener. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1038\/nm1066","article-title":"Protein Aggregation and Neurodegenerative Disease","volume":"10","author":"Ross","year":"2004","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s Disease: Mechanisms and Models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13621","DOI":"10.1074\/jbc.M109.074617","article-title":"Lysosomal Degradation of Alpha-Synuclein in Vivo","volume":"285","author":"Mak","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"25009","DOI":"10.1074\/jbc.M300227200","article-title":"Alpha-Synuclein Is Degraded by Both Autophagy and the Proteasome","volume":"278","author":"Webb","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1126\/science.1101738","article-title":"Impaired Degradation of Mutant Alpha-Synuclein by Chaperone-Mediated Autophagy","volume":"305","author":"Cuervo","year":"2004","journal-title":"Science"},{"key":"ref_22","first-page":"777","article-title":"Dopamine-Modified Alpha-Synuclein Blocks Chaperone-Mediated Autophagy","volume":"118","author":"Talloczy","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Xilouri, M., Vogiatzi, T., Vekrellis, K., Park, D., and Stefanis, L. (2009). Abberant Alpha-Synuclein Confers Toxicity to Neurons in Part through i Nhibition of Chaperone-Mediated Autophagy. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005515"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6139","DOI":"10.1093\/hmg\/ddu334","article-title":"Genetic Analysis Implicates APOE, SNCA and Suggests Lysosomal Dysfunction in the Etiology of Dementia with Lewy Bodies","volume":"23","author":"Bras","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1080\/15548627.2015.1067364","article-title":"Genetic Perspective on the Role of the Autophagy-Lysosome Pathway in Parkinson Disease","volume":"11","author":"Dion","year":"2015","journal-title":"Autophagy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/ane.12563","article-title":"The Genetic Background of Parkinson\u2019s Disease: Current Progress and Future Prospects","volume":"134","author":"Kalinderi","year":"2016","journal-title":"Acta Neurol. Scand."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1038\/s41418-022-01028-6","article-title":"Past, Present, and Future Perspectives of Transcription Factor EB (TFEB): Mechanisms of Regulation and Association with Disease","volume":"29","author":"Tan","year":"2022","journal-title":"Cell Death Differ."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.1204592","article-title":"TFEB Links Autophagy to Lysosomal Biogenesis","volume":"332","author":"Settembre","year":"2011","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E1817","DOI":"10.1073\/pnas.1305623110","article-title":"TFEB-Mediated Autophagy Rescues Midbrain Dopamine Neurons from \u03b1-Synuclein Toxicity","volume":"110","author":"Decressac","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kilpatrick, K., Zeng, Y., Hancock, T., and Segatori, L. (2015). Genetic and Chemical Activation of TFEB Mediates Clearance of Aggregated \u03b1-Synuclein. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120819"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.15252\/emmm.201303671","article-title":"Selective Clearance of Aberrant Tau Proteins and Rescue of Neurotoxicity by Transcription Factor EB","volume":"6","author":"Polito","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"12137","DOI":"10.1523\/JNEUROSCI.0705-15.2015","article-title":"Neuronal-Targeted TFEB Accelerates Lysosomal Degradation of APP, Reducing A\u03b2 Generation and Amyloid Plaque Pathogenesis","volume":"35","author":"Xiao","year":"2015","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9607","DOI":"10.1523\/JNEUROSCI.3788-13.2014","article-title":"Enhancing Astrocytic Lysosome Biogenesis Facilitates A\u03b2 Clearance and Attenuates Amyloid Plaque Pathogenesis","volume":"34","author":"Xiao","year":"2014","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"142ra97","DOI":"10.1126\/scitranslmed.3003799","article-title":"PGC-1\u03b1 Rescues Huntington\u2019s Disease Proteotoxicity by Preventing Oxidative Stress and Promoting TFEB Function","volume":"4","author":"Tsunemi","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.ymthe.2018.02.022","article-title":"Overexpression of TFEB Drives a Pleiotropic Neurotrophic Effect and Prevents Parkinson\u2019s Disease-Related Neurodegeneration","volume":"26","author":"Torra","year":"2018","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1111\/ajt.13151","article-title":"Evolving Perspectives of mTOR Complexes in Immunity and Transplantation","volume":"15","author":"Fantus","year":"2015","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1111\/bcp.12893","article-title":"New Perspectives on mTOR Inhibitors (Rapamycin, Rapalogs and TORKinibs) in Transplantation","volume":"82","author":"Waldner","year":"2016","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14338","DOI":"10.1038\/ncomms14338","article-title":"mTORC1-Independent TFEB Activation via Akt Inhibition Promotes Cellular Clearance in Neurodegenerative Storage Diseases","volume":"8","author":"Palmieri","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_39","first-page":"3","article-title":"The Blood-Brain Barrier: Bottleneck in Brain Drug Development","volume":"2","author":"Pardridge","year":"2005","journal-title":"NeuroRx J. Am. Soc. Exp. Neurother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8023","DOI":"10.1074\/jbc.M900301200","article-title":"An ATP-Competitive Mammalian Target of Rapamycin Inhibitor Reveals Rapamycin-Resistant Functions of mTORC1","volume":"284","author":"Thoreen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1080\/15548627.2016.1271514","article-title":"Multistep Regulation of TFEB by MTORC1","volume":"13","author":"Konda","year":"2017","journal-title":"Autophagy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"903","DOI":"10.4161\/auto.19653","article-title":"MTORC1 Functions as a Transcriptional Regulator of Autophagy by Preventing Nuclear Transport of TFEB","volume":"8","author":"Martina","year":"2012","journal-title":"Autophagy"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1038\/emboj.2012.32","article-title":"A Lysosome-to-Nucleus Signalling Mechanism Senses and Regulates the Lysosome via mTOR and TFEB","volume":"31","author":"Settembre","year":"2012","journal-title":"EMBO J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1101\/gad.213827.113","article-title":"A RANKL-PKC\u03b2-TFEB Signaling Cascade Is Necessary for Lysosomal Biogenesis in Osteoclasts","volume":"27","author":"Ferron","year":"2013","journal-title":"Genes Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12964-020-00636-4","article-title":"Calcineurin","volume":"18","author":"Creamer","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"R442","DOI":"10.1016\/j.cub.2005.06.006","article-title":"Calcineurin","volume":"15","author":"Hogan","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/ncb3114","article-title":"Lysosomal Calcium Signalling Regulates Autophagy through Calcineurin and TFEB","volume":"17","author":"Medina","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.1174447","article-title":"A Gene Network Regulating Lysosomal Biogenesis and Function","volume":"325","author":"Sardiello","year":"2009","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.4161\/auto.7.11.17166","article-title":"TFEB Regulates Autophagy: An Integrated Coordination of Cellular Degradation and Recycling Processes","volume":"7","author":"Settembre","year":"2011","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a Mammalian Homologue of Yeast Apg8p, Is Localized in Autophagosome Membranes after Processing","volume":"19","author":"Kabeya","year":"2000","journal-title":"EMBO J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine Inhibits Autophagic Flux by Decreasing Autophagosome-Lysosome Fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/s41580-024-00757-5","article-title":"Mechanisms of Autophagy-Lysosome Dysfunction in Neurodegenerative Diseases","volume":"25","author":"Nixon","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00401-012-1004-6","article-title":"Protein Degradation Pathways in Parkinson\u2019s Disease: Curse or Blessing","volume":"124","author":"Wahlster","year":"2012","journal-title":"Acta Neuropathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tcb.2014.05.003","article-title":"Proteostasis Impairment in Protein-Misfolding and -Aggregation Diseases","volume":"24","author":"Hipp","year":"2014","journal-title":"Trends Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102584","DOI":"10.1016\/j.arr.2024.102584","article-title":"Targeted Protein Degradation: Expanding the Technology to Facilitate the Clearance of Neurotoxic Proteins in Neurodegenerative Diseases","volume":"102","author":"Wang","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd.2018.109","article-title":"Promoting the Clearance of Neurotoxic Proteins in Neurodegenerative Disorders of Ageing","volume":"17","author":"Boland","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40035-017-0077-5","article-title":"Protein Misfolding in Neurodegenerative Diseases: Implications and Strategies","volume":"6","author":"Sweeney","year":"2017","journal-title":"Transl. Neurodegener."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1146\/annurev-neuro-070815-014031","article-title":"Brain Disorders Due to Lysosomal Dysfunction","volume":"39","author":"Fraldi","year":"2016","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/alz.12776","article-title":"Inhibition of the Dopamine Transporter Promotes Lysosome Biogenesis and Ameliorates Alzheimer\u2019s Disease\u2013like Symptoms in Mice","volume":"19","author":"Yin","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.nbd.2014.05.009","article-title":"Immunotherapy Targeting \u03b1-Synuclein Protofibrils Reduced Pathology in (Thy-1)-h[A30P] \u03b1-Synuclein Mice","volume":"69","author":"Fagerqvist","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Shahaduzzaman, M., Nash, K., Hudson, C., Sharif, M., Grimmig, B., Lin, X., Bai, G., Liu, H., Ugen, K.E., and Cao, C. (2015). Anti-Human \u03b1-Synuclein N-Terminal Peptide Antibody Protects against Dopaminergic Cell Death and Ameliorates Behavioral Deficits in an AAV-\u03b1-Synuclein Rat Model of Parkinson\u2019s Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116841"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13454","DOI":"10.1523\/JNEUROSCI.1292-12.2012","article-title":"Antibody-Aided Clearance of Extracellular \u03b1-Synuclein Prevents Cell-to-Cell Aggregate Transmission","volume":"32","author":"Bae","year":"2012","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-015-0008-9","article-title":"Active Immunization against Alpha-Synuclein Ameliorates the Degenerative Pathology and Prevents Demyelination in a Model of Multiple System Atrophy","volume":"10","author":"Mandler","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1016\/j.celrep.2014.05.033","article-title":"A-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded \u03b1-Synuclein and Neurodegeneration","volume":"7","author":"Tran","year":"2014","journal-title":"Cell Rep."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Caramiello, A.M., and Pirota, V. (2024). Novel Therapeutic Horizons: SNCA Targeting in Parkinson\u2019s Disease. Biomolecules, 14.","DOI":"10.3390\/biom14080949"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.actbio.2024.01.019","article-title":"Biomimetic Nanodecoys Deliver Cholesterol-Modified Heteroduplex Oligonucleotide to Target Dopaminergic Neurons for the Treatment of Parkinson\u2019s Disease","volume":"177","author":"Huang","year":"2024","journal-title":"Acta Biomater."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e135633","DOI":"10.1172\/jci.insight.135633","article-title":"\u03b1-Synuclein Antisense Oligonucleotides as a Disease-Modifying Therapy for Parkinson\u2019s Disease","volume":"6","author":"Cole","year":"2021","journal-title":"JCI Insight"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:19:17Z","timestamp":1768713557000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,16]]},"references-count":67,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020905"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020905","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,16]]}}}