{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTau tubulin kinase 2 (TTBK2) is a multifunctional serine/threonine kinase that plays a pivotal role in initiating and regulating ciliogenesis. At the onset of cilia formation, TTBK2 is recruited to the distal end of the mother centriole by interacting with distal appendage proteins such as CEP164. Once there, its kinase activity promotes the removal of the inhibitory protein CP110 and the subsequent recruitment of intraflagellar transport proteins, thereby triggering ciliary vesicle docking and axoneme elongation. TTBK2 also phosphorylates several key substrates—including CEP83, CEP97, and other ciliary components—to coordinate early steps that ensure proper cilia assembly and stability, a process further modulated by upstream regulators like CSNK2A1 that fine‐tune ciliary length and trafficking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, aberrations in TTBK2 activity underlie neurodegenerative changes, most notably in spinocerebellar ataxia type 11 (SCA11). Mutations in TTBK2—often resulting in truncated proteins—are linked to cerebellar degeneration, tau pathology, and TDP‐43 proteinopathies. Such mutant forms of TTBK2 can act in a dominant–negative manner, interfering with the wild–type enzyme’s ciliogenic and signaling functions, thereby impairing Sonic hedgehog (SHH) pathway activity and potentially altering glutamate receptor regulation. Genetic screening studies have underscored the heterogeneity of autosomal dominant cerebellar ataxias and confirmed a pathogenic role for TTBK2 mutations in diverse patient cohorts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates TTBK2 in oncogenic processes. In various tumor models, altered expression of TTBK2—and even circular RNA species derived from the TTBK2 gene (circ‐TTBK2)—has been associated with enhanced tumor cell survival, chemotherapeutic resistance, and altered cellular metabolism through regulation of Na⁺–coupled glucose transporters. These cancer–related roles extend the functional repertoire of TTBK2 well beyond its established contributions to cilia formation and neuronal integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in cilia assembly and tumor biology, TTBK2 regulates cytoskeletal dynamics by functioning as a microtubule plus–end tracking protein (+TIP). Through its interaction with end–binding proteins and phosphorylation of targets such as the MT–depolymerizing kinesin KIF2A, TTBK2 modulates microtubule stability and cell migration. Its capacity to phosphorylate both tau and tubulin underscores an important role in maintaining neuronal cytoskeletal integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sarah C Goetz, Karel F Liem, Kathryn V Anderson "}, {"type": "b", "children": [{"type": "t", "text": "The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2012.10.010"}], "href": "https://doi.org/10.1016/j.cell.2012.10.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23141541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23141541"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lukáš Čajánek, Erich A Nigg "}, {"type": "b", "children": [{"type": "t", "text": "Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1401777111"}], "href": "https://doi.org/10.1073/pnas.1401777111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24982133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24982133"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Toshiaki Oda, Shuhei Chiba, Tomoaki Nagai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Binding to Cep164, but not EB1, is essential for centriolar localization of TTBK2 and its function in ciliogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12191"}], "href": "https://doi.org/10.1111/gtc.12191"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25297623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25297623"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chien-Hui Lo, I-Hsuan Lin, T Tony Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201811142"}], "href": "https://doi.org/10.1083/jcb.201811142"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31455668"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31455668"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ondrej Bernatik, Petra Pejskova, David Vyslouzil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin kinase 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E19-06-0334"}], "href": "https://doi.org/10.1091/mbc.E19-06-0334"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32129703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32129703"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Abdelhalim Loukil, Chloe Barrington, Sarah C Goetz "}, {"type": "b", "children": [{"type": "t", "text": "A complex of distal appendage-associated kinases linked to human disease regulates ciliary trafficking and stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2018740118"}], "href": "https://doi.org/10.1073/pnas.2018740118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33846249"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33846249"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ivan Rosa E Silva, Lucia Binó, Christopher M Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanisms underlying the role of the centriolar CEP164-TTBK2 complex in ciliopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2021.08.007"}], "href": "https://doi.org/10.1016/j.str.2021.08.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34499853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34499853"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Alfredo Brusco, Cinzia Gellera, Claudia Cagnoli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Neurol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/archneur.61.5.727"}], "href": "https://doi.org/10.1001/archneur.61.5.727"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15148151"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15148151"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Henry Houlden, Janel Johnson, Christopher Gardner-Thorpe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2007.43"}], "href": "https://doi.org/10.1038/ng.2007.43"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18037885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18037885"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ulf Edener, Ingo Kurth, Annechristin Meiner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense exchanges in the TTBK2 gene mutated in SCA11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00415-009-5209-0"}], "href": "https://doi.org/10.1007/s00415-009-5209-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19533200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19533200"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Qian Xu, Xiaohui Li, Junling Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spinocerebellar ataxia type 11 in the Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10072-009-0129-4"}], "href": "https://doi.org/10.1007/s10072-009-0129-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19768375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19768375"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Peter Bauer, Giovanni Stevanin, Christian Beetz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurol Neurosurg Psychiatry (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jnnp.2009.202150"}], "href": "https://doi.org/10.1136/jnnp.2009.202150"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20667868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20667868"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Nicole F Liachko, Pamela J McMillan, Timothy J Strovas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The tau tubulin kinases TTBK1/2 promote accumulation of pathological TDP-43."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1004803"}], "href": "https://doi.org/10.1371/journal.pgen.1004803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25473830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25473830"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Kristina Nieding, Veronika Matschke, Sven G Meuth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tau Tubulin Kinase TTBK2 Sensitivity of Glutamate Receptor GluK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000447847"}], "href": "https://doi.org/10.1159/000447847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27607061"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27607061"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Emily Bowie, Ryan Norris, Kathryn V Anderson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spinocerebellar ataxia type 11-associated alleles of Ttbk2 dominantly interfere with ciliogenesis and cilium stability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1007844"}], "href": "https://doi.org/10.1371/journal.pgen.1007844"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30532139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30532139"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Daniela Felício, Mariana Santos "}, {"type": "b", "children": [{"type": "t", "text": "Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cerebellum (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12311-023-01540-6"}], "href": "https://doi.org/10.1007/s12311-023-01540-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36892783"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36892783"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Frances M Bashore, Ariana B Marquez, Apirat Chaikuad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-023-32854-4"}], "href": "https://doi.org/10.1038/s41598-023-32854-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37059819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37059819"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Yin-Qian Lu, Jian-Min Chen, Ya-Li Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel TTBK2 Mutation in a Chinese Pedigree with Spinocerebellar Ataxia 11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cerebellum (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12311-023-01616-3"}], "href": "https://doi.org/10.1007/s12311-023-01616-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37848700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37848700"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Claus Bender, Axel Ullrich "}, {"type": "b", "children": [{"type": "t", "text": "PRKX, TTBK2 and RSK4 expression causes Sunitinib resistance in kidney carcinoma- and melanoma-cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.26486"}], "href": "https://doi.org/10.1002/ijc.26486"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22020623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22020623"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Ioana Alesutan, Mentor Sopjani, Miribane Dërmaku-Sopjani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of Na-coupled glucose transporter SGLT1 by Tau tubulin kinase 2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000339039"}], "href": "https://doi.org/10.1159/000339039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22814243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22814243"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Jian Zheng, Xiaobai Liu, Yixue Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1β/Derlin-1 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hematol Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13045-017-0422-2"}], "href": "https://doi.org/10.1186/s13045-017-0422-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28219405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28219405"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "D-H Yuan, J Zhao, G-F Shao "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA TTBK2 promotes the development of human glioma cells via miR-520b/EZH2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_201912_19792"}], "href": "https://doi.org/10.26355/eurrev_201912_19792"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31858557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31858557"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "H-Y Zhang, B-W Zhang, Z-B Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA TTBK2 regulates cell proliferation, invasion and ferroptosis via miR-761/ITGB8 axis in glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Rev Med Pharmacol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.26355/eurrev_202003_20528"}], "href": "https://doi.org/10.26355/eurrev_202003_20528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32196629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32196629"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Jung-Chi Liao, T Tony Yang, Rueyhung Roc Weng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TTBK2: a tau protein kinase beyond tau phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/575170"}], "href": "https://doi.org/10.1155/2015/575170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25950000"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25950000"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Takashi Watanabe, Mai Kakeno, Toshinori Matsui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TTBK2 with EB1/3 regulates microtubule dynamics in migrating cells through KIF2A phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201412075"}], "href": "https://doi.org/10.1083/jcb.201412075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26323690"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26323690"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Laura M Taylor, Pamela J McMillan, Nicole F Liachko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurodegener (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13024-018-0237-9"}], "href": "https://doi.org/10.1186/s13024-018-0237-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29409526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29409526"}]}]}]}