{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:24:17Z","timestamp":1783441457390,"version":"3.54.6"},"reference-count":108,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are uncommon multifactorial atypical Parkinsonian syndromes, expressed by various clinical features. MSA and PSP are commonly considered sporadic neurodegenerative disorders; however, our understanding is improving of their genetic framework. The purpose of this study was to critically review the genetics of MSA and PSP and their involvement in the pathogenesis. A systemized literature search of PubMed and MEDLINE was performed up to 1 January 2023. Narrative synthesis of the results was undertaken. In total, 43 studies were analyzed. Although familial MSA cases have been reported, the hereditary nature could not be demonstrated. COQ2 mutations were involved in familial and sporadic MSA, without being reproduced in various clinical populations. In terms of the genetics of the cohort, synuclein alpha (SNCA) polymorphisms were correlated with an elevated likelihood of manifesting MSA in Caucasians, but a causal effect relationship could not be demonstrated. Fifteen MAPT mutations were linked with PSP. Leucine-rich repeat kinase 2 (LRRK2) is an infrequent monogenic mutation of PSP. Dynactin subunit 1 (DCTN1) mutations may imitate the PSP phenotype. GWAS have noted many risk loci of PSP (STX6 and EIF2AK3), suggesting pathogenetic mechanisms related to PSP. Despite the limited evidence, it seems that genetics influence the susceptibility to MSA and PSP. MAPT mutations result in the MSA and PSP pathologies. Further studies are crucial to elucidate the pathogeneses of MSA and PSP, which will support efforts to develop novel drug options.<\/jats:p>","DOI":"10.3390\/ijms24065281","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T02:30:33Z","timestamp":1678415433000},"page":"5281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetics of Multiple System Atrophy and Progressive Supranuclear Palsy: A Systemized Review of the Literature"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3006-8711","authenticated-orcid":false,"given":"Anastasia","family":"Bougea","sequence":"first","affiliation":[{"name":"1st Department of Neurology, Medical School, Eginition Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/WCO.0000000000000581","article-title":"Progressive supranuclear palsy and multiple system atrophy: Clinicopathological concepts and therapeutic challenges","volume":"31","author":"Respondek","year":"2018","journal-title":"Curr. Opin. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fneur.2020.00180","article-title":"Progressive Supranuclear Palsy-Parkinsonism Predominant (PSP-P)-A Clinical Challenge at the Boundaries of PSP and Parkinson\u2019s Disease (PD)","volume":"11","author":"Alster","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.autneu.2017.10.007","article-title":"Diagnosis of multiple system atrophy","volume":"211","author":"Palma","year":"2018","journal-title":"Auton. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1093\/brain\/122.7.1233","article-title":"Clinical genetics of familial progressive supranuclear palsy","volume":"122","author":"Rojo","year":"1999","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.parkreldis.2014.10.028","article-title":"Three sib-pairs of autopsy-confirmed progressive supranuclear palsy","volume":"21","author":"Fujioka","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/ana.20449","article-title":"Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1","volume":"57","author":"Ros","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1001\/archneur.64.4.545","article-title":"Multiplex families with multiple system atrophy","volume":"64","author":"Hara","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_8","first-page":"449","article-title":"Definite multiple system atrophy in a German family","volume":"80","author":"Schmitt","year":"2009","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.jocn.2011.06.018","article-title":"Probable hereditary multiple system atrophy-autonomic (MSA-A) in a family in the United States","volume":"19","author":"Hohler","year":"2012","journal-title":"J. Clin. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jns.2005.09.003","article-title":"Heredity in multiple system atrophy","volume":"240","author":"Soma","year":"2006","journal-title":"J. Neurol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/s41598-018-19198-0","article-title":"Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome","volume":"8","author":"Yabe","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13195-017-0330-2","article-title":"Slowly progressive dementia caused by MAPT R406W mutations: Longitudinal report on a new kindred and systematic review","volume":"10","author":"Ygland","year":"2018","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ana.410390214","article-title":"Spinocerebellar ataxia type 1 with multiple system degeneration and glial cytoplasmic inclusions","volume":"39","author":"Gilman","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1212\/WNL.0b013e318294b2eb","article-title":"Similarities between familial and sporadic autopsy-proven progressive supranuclear palsy","volume":"80","author":"Fujioka","year":"2013","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1212\/WNL.0b013e3181a92bcc","article-title":"Familial aggregation of parkinsonism in progressive supranuclear palsy","volume":"73","author":"Boon","year":"2009","journal-title":"Neurology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1002\/mds.27702","article-title":"Genome-wide survey of copy number variants finds MAPT duplications in progressive supranuclear palsy","volume":"34","author":"Chen","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1212\/WNL.0000000000003221","article-title":"European Multiple System Atrophy Study Group and the UK Multiple System Atrophy Study Group A genome-wide association study in multiple system atrophy","volume":"87","author":"Sailer","year":"2016","journal-title":"Neurology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40478-019-0769-4","article-title":"Cross-examining candidate genes implicated in multiple system atrophy","volume":"7","author":"Katzeff","year":"2019","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_19","first-page":"93","article-title":"Genetics of Progressive Supranuclear Palsy: A Review","volume":"11","author":"Wen","year":"2021","journal-title":"J. Park. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1471-1842.2009.00848.x","article-title":"A typology of reviews: An analysis of 14 review types and associated methodologies","volume":"26","author":"Grant","year":"2009","journal-title":"Health Inf. Libr. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1136\/bmj.38636.593461.68","article-title":"Effectiveness and efficiency of search methods in systematic reviews of complex evidence: Audit of primary sources","volume":"331","author":"Greenhalgh","year":"2005","journal-title":"BMJ"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/bs.acc.2020.08.007","article-title":"Synuclein in neurodegeneration","volume":"103","author":"Bougea","year":"2020","journal-title":"Adv. Clin. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S53","DOI":"10.1002\/mds.20540","article-title":"In vitro models of multiple system atrophy","volume":"20","author":"Stefanova","year":"2005","journal-title":"Mov. Disord."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S1474-4422(19)30287-X","article-title":"The genetic architecture of Parkinson\u2019s disease","volume":"19","author":"Blauwendraat","year":"2020","journal-title":"Lancet Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00401-013-1096-7","article-title":"Alpha-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson\u2019s disease and multiple system atrophy?","volume":"125","author":"Kiely","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13024-015-0038-3","article-title":"Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation","volume":"10","author":"Kiely","year":"2015","journal-title":"Mol. Neurodegener."},{"key":"ref_27","first-page":"e2181","article-title":"Novel alpha-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson\u2019s disease-type pathology","volume":"35","author":"Pasanen","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/mds.23455","article-title":"Glia: Initiators and progressors of pathology in Parkinson\u2019s disease","volume":"26","author":"Halliday","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Al-Chalabi, A., D\u00fcrr, A., Wood, N.W., Parkinson, M.H., Camuzat, A., Hulot, J.S., Morrison, K.E., Renton, A., Sussmuth, S.D., and Landwehrmeyer, B.G. (2009). NNIPPS Genetic Study Group. Genetic variants of the alpha-synuclein gene SNCA are associated with multiple system atrophy. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007114"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/ana.21685","article-title":"SNCA variants are associated with increased risk for multiple system atrophy","volume":"65","author":"Scholz","year":"2009","journal-title":"Ann. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, Y., Wei, Q.Q., Ou, R., Cao, B., Chen, X., Zhao, B., Guo, X., Yang, Y., Chen, K., and Wu, Y. (2015). Genetic Variants of SNCA Are Associated with Susceptibility to Parkinson\u2019s Disease but Not Amyotrophic Lateral Sclerosis or Multiple System Atrophy in a Chinese Population. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133776"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Mantle, D., and Hargreaves, I.P. (2022). Coenzyme Q10: Role in Less Common Age-Related Disorders. Antioxidants, 11.","DOI":"10.3390\/antiox11112293"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"117623","DOI":"10.1016\/j.jns.2021.117623","article-title":"COQ2 V393A confers high risk susceptibility for multiple system atrophy in East Asian population","volume":"429","author":"Porto","year":"2021","journal-title":"J. Neurol. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1056\/NEJMc1311763","article-title":"Mutant COQ2 in multiplesystem atrophy","volume":"371","author":"Jeon","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s00702-018-1885-1","article-title":"COQ2 variants in Parkinson\u2019s disease and multiple system atrophy","volume":"125","author":"Mikasa","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_36","first-page":"81","article-title":"Mutant COQ2 in multiple-system atrophy","volume":"371","author":"Schottlaender","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Multiple-System Atrophy Research Collaboration (2013). Mutations in COQ2 in familial and sporadic multiple-system atrophy. N. Engl. J. Med., 369, 233\u2013244.","DOI":"10.1056\/NEJMoa1212115"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1212\/NXG.0000000000000054","article-title":"New susceptible variant ofCOQ2gene in Japanese patients with sporadic multiple system atrophy","volume":"2","author":"Sun","year":"2016","journal-title":"Neurol. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/cns.12412","article-title":"Mutation analysis of COQ2 in Chinese patients with cerebellar subtype of multiple system atrophy","volume":"21","author":"Wen","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kasai, T., Tokuda, T., Ohmichi, T., Ishii, R., Tatebe, H., Nakagawa, M., and Mizuno, T. (2016). Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147574"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.parkreldis.2018.07.017","article-title":"Clinical correlates of decreased plasma coenzyme Q10 levels in patients with multiple system atrophy","volume":"57","author":"Du","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.parkreldis.2017.10.010","article-title":"Cerebrospinal fluid levels of coenzyme Q10 are reduced in multiple system atrophy","volume":"46","author":"Compta","year":"2017","journal-title":"Park. Relat. Disord."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/jnen\/nlw037","article-title":"Decreased Coenzyme Q10 Levels in Multiple System Atrophy Cerebellum","volume":"75","author":"Barca","year":"2016","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1073\/pnas.72.5.1858","article-title":"A protein factor essential for microtubule assembly","volume":"72","author":"Weingarten","year":"1975","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fnagi.2019.00204","article-title":"Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects","volume":"11","author":"Barbier","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0304-3940(97)00474-6","article-title":"Tau protein in the glial cytoplasmic inclusions of multiple system atrophy can be distinguished from abnormal tau in Alzheimer\u2019s disease","volume":"230","author":"Cairns","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"547.e11","DOI":"10.1016\/j.neurobiolaging.2009.09.011","article-title":"Different MAPT haplotypes are associated with Parkinson\u2019s disease and progressive supranuclear palsy","volume":"32","author":"Ezquerra","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/alzrt268","article-title":"Association of MAPT haplotypes with Alzheimer\u2019s disease risk and MAPT brain gene expression levels","volume":"6","author":"Allen","year":"2014","journal-title":"Alzheimers Res. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1212\/WNL.0b013e31820c30c1","article-title":"MAPT H1 haplotype is a risk factor for essential tremor and multiple system atrophy","volume":"76","author":"Rajput","year":"2011","journal-title":"Neurology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.parkreldis.2016.06.010","article-title":"MAPT haplotype diversity in multiple system atrophy","volume":"30","author":"Heckman","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1007\/s00702-022-02531-3","article-title":"Glucocerebrosidase mutations and Parkinson disease","volume":"129","author":"Vieira","year":"2022","journal-title":"J. Neural Transm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/acn3.185","article-title":"Variants associated with Gaucher disease in multiple system atrophy","volume":"2","author":"Mitsui","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/mdc3.12481","article-title":"Frequency of GBA Variants in Autopsy-proven Multiple System Atrophy","volume":"4","author":"Sklerov","year":"2017","journal-title":"Mov. Disord. Clin. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1212\/01.wnl.0000345356.40399.eb","article-title":"Glucocerebrosidase mutations in 108 neuropathologically confirmed cases of multiple system atrophy","volume":"72","author":"Segarane","year":"2009","journal-title":"Neurology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jocn.2012.01.055","article-title":"Genetic association study of glucocerebrosidase gene L444P mutation in essential tremor and multiple system atrophy in mainland China","volume":"20","author":"Sun","year":"2013","journal-title":"J. Clin. Neurosci."},{"key":"ref_56","first-page":"e5","article-title":"MSA Exome Consortium Lysosomal storage disorder gene variants in multiple system atrophy","volume":"141","author":"Schottlaender","year":"2018","journal-title":"Brain"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.parkreldis.2020.06.007","article-title":"GBA variation and susceptibility to multiple system atrophy","volume":"77","author":"Wernick","year":"2020","journal-title":"Park. Relat. Disord."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1042\/EBC20210013","article-title":"LRRK2 signaling in neurodegeneration: Two decades of progress","volume":"65","author":"Iannotta","year":"2021","journal-title":"Essays Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e00660-20","DOI":"10.1128\/MCB.00660-20","article-title":"The Cell Biology of LRRK2 in Parkinson\u2019s Disease","volume":"41","author":"Usmani","year":"2021","journal-title":"Mol. Cell. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1002\/mds.21343","article-title":"G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy","volume":"22","author":"Ozelius","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.parkreldis.2014.11.022","article-title":"An association analysis of the R1628P and G2385R polymorphisms of the LRRK2 gene in multiple system atrophy in a Chinese population","volume":"21","author":"Yuan","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1212\/WNL.0000000000001078","article-title":"LRRK2 exonic variants and risk of multiple system atrophy","volume":"83","author":"Heckman","year":"2014","journal-title":"Neurology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/mds.27710","article-title":"Early-onset pathologically proven multiple system atrophy with LRRK2 G2019S mutation","volume":"34","author":"Riboldi","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS","volume":"72","author":"Mackenzie","year":"2011","journal-title":"Neuron"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1223.e1","DOI":"10.1016\/j.neurobiolaging.2014.08.033","article-title":"Multiple system atrophy is not caused by C9orf72 hexanucleotide repeat expansions","volume":"36","author":"Scholz","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1007\/s00702-016-1598-2","article-title":"C9ORF72 repeat expansions in Chinese patients with Parkinson\u2019s disease and multiple system atrophy","volume":"123","author":"Chen","year":"2016","journal-title":"J. Neural Transm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.neurobiolaging.2014.08.024","article-title":"Analysis of C9orf72 repeat expansions in a large series of clinically and pathologically diagnosed cases with atypical parkinsonism","volume":"36","author":"Schottlaender","year":"2015","journal-title":"Neurobiol. Aging."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1001\/jamaneurol.2013.5762","article-title":"Multiple system atrophy and amyotrophic lateral sclerosis in a family with hexanucleotide repeat expansions in C9orf72","volume":"71","author":"Goldman","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1007\/s00415-015-7873-6","article-title":"C9ORF72 intermediate repeat expansion in patients affected by atypical parkinsonian syndromes or Parkinson\u2019s disease complicated by psychosis or dementia in a Sardinian population","volume":"262","author":"Cannas","year":"2015","journal-title":"J. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.neurobiolaging.2021.12.003","article-title":"Multiple system atrophy and C9orf72 hexanucleotide repeat expansions in a cohort of Italian patients","volume":"112","author":"Bonapace","year":"2021","journal-title":"Neurobiol. Aging"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/neup.12808","article-title":"A pathologically confirmed case of combined amyotrophic lateral sclerosis with C9orf72 mutation and multiple system atrophy","volume":"42","author":"King","year":"2022","journal-title":"Neuropathology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1002\/ana.10340","article-title":"An R5L tau mutation in a subject with a progressive supranuclear palsy phenotype","volume":"52","author":"Poorkaj","year":"2002","journal-title":"Ann. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1212\/WNL.53.4.864","article-title":"A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration","volume":"53","author":"Yasuda","year":"1999","journal-title":"Neurology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s004010051052","article-title":"A mutation at codon 279 (N279K) in exon 10 of the Tau gene causes a tauopathy with dementia and supranuclear palsy","volume":"98","author":"Delisle","year":"1999","journal-title":"Acta Neuropathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1001\/archneur.60.10.1454","article-title":"A Case of Dementia Parkinsonism Resembling Progressive Supranuclear Palsy Due to Mutation in the Tau Protein Gene","volume":"60","author":"Soliveri","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.parkreldis.2012.06.019","article-title":"Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS","volume":"19","author":"Ogaki","year":"2013","journal-title":"Park. Relat. Disord."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/mds.23461","article-title":"Visual grasping in frontotemporal dementia and parkinsonism linked to chromosome 17 (microtubule-associated with protein tau): A comparison of N-Isopropyl-p- [(123)I]-iodoamphetamine brain perfusion single photon emission computed tomography analysis with progressive supranuclear palsy","volume":"26","author":"Ogaki","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000319454","article-title":"Novel L284R MAPT Mutation in a Family with an Autosomal Dominant Progressive Supranuclear Palsy Syndrome","volume":"8","author":"Rohrer","year":"2010","journal-title":"Neurodegener. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1002\/1531-8249(20010201)49:2<263::AID-ANA50>3.0.CO;2-K","article-title":"Familial atypical progres sive supranuclear palsy associated with homozigosity for the deln296 mutation in the tau gene","volume":"49","author":"Pastor","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1002\/ana.20006","article-title":"Progressive supranuclear palsy and Parkinson\u2019s disease in a family with a new mutation in the tau gene","volume":"55","author":"Rossi","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"240.e13","DOI":"10.1016\/j.neurobiolaging.2019.02.016","article-title":"Tau aggregation and seeding analyses of two novel MAPT variants found in patients with motor neuron disease and progressive parkinsonism","volume":"84","author":"Nakayama","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/brain\/122.4.741","article-title":"A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L)","volume":"122","author":"Bird","year":"1999","journal-title":"Brain"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1001\/archneur.62.9.1444","article-title":"A New Mutation of the \u03c4 Gene, G303V, in Early-Onset Familial Progressive Supranuclear Palsy","volume":"62","author":"Ros","year":"2005","journal-title":"Arch. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/brain\/123.5.880","article-title":"Progressive supranuclear palsy pathology caused by a novel silent mutation in exon 10 of the tau gene: Expansion of the disease phenotype caused by tau gene mutations","volume":"123","author":"Stanford","year":"2000","journal-title":"Brain"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/brain\/awm280","article-title":"The tauopathy associated with mutation+3 in intron 10 of Tau: Characterization of the MSTD family","volume":"131","author":"Spina","year":"2008","journal-title":"Brain"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1212\/WNL.0b013e318248e531","article-title":"Autosomal dominant tauopathy with parkinsonism and central hypoventilation","volume":"78","author":"Omoto","year":"2012","journal-title":"Neurology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1212\/01.WNL.0000072325.27824.A5","article-title":"Tau exon 10 +16 mutation FTDP-17 presenting clinically as sporadic young onset PSP","volume":"61","author":"Morris","year":"2003","journal-title":"Neurology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.neurobiolaging.2013.08.004","article-title":"Different mutations at V363 MAPT codon are associated with atypical clinical phenotypes and show unusual structural and functional features","volume":"35","author":"Rossi","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13024-018-0267-3","article-title":"Replication of progressive supranuclear palsy genome-wide association study identifies SLCO1A2 and DUSP10 as new susceptibility loci","volume":"13","author":"Kouri","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13024-018-0270-8","article-title":"Joint genome-wide association study of progressive supranuclear palsy identifies novel susceptibility loci and genetic correlation to neurodegenerative diseases","volume":"13","author":"Chen","year":"2018","journal-title":"Mol. Neurodegener."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/ng.859","article-title":"Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy","volume":"43","author":"Melhem","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1474-4422(20)30394-X","article-title":"Genetic determinants of survival in progressive supranuclear palsy: A genome-wide association study","volume":"20","author":"Jabbari","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuron.2004.11.005","article-title":"Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology","volume":"44","author":"Zimprich","year":"2004","journal-title":"Neuron"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1212\/01.WNL.0000125015.06989.DB","article-title":"Autosomal dominant parkinsonism associated with variable synuclein and tau pathology","volume":"62","author":"Wszolek","year":"2004","journal-title":"Neurology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1212\/01.wnl.0000239829.33936.73","article-title":"LRRK2 mutations on Crete: R1441H associated with PD evolving to PSP","volume":"67","author":"Spanaki","year":"2006","journal-title":"Neurology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1111\/j.1468-1331.2009.02702.x","article-title":"Screening forLRRK2R1441 mutations in a cohort of PSP patients from Germany","volume":"16","author":"Schulte","year":"2009","journal-title":"Eur. J. Neurol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1212\/01.wnl.0000240220.33950.0c","article-title":"Parkinsonism, Lrrk2 G2019S, and tau neuropathology","volume":"67","author":"Rajput","year":"2006","journal-title":"Neurology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1365-2990.2011.01216.x","article-title":"Atypical tauopathy in a patient with LRRK2-G2019S mutation and tremor-dominant Parkinsonism","volume":"38","author":"Ruffmann","year":"2011","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_99","first-page":"e211","article-title":"Genetic analysis of neurodegenerative diseases in a pathology cohort","volume":"76","author":"Blauwendraat","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.parkreldis.2015.07.011","article-title":"Novel LRRK2 mutations in Parkinsonism","volume":"21","author":"Trinh","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"ref_101","first-page":"115","article-title":"Study of LRRK2 variation in tauopathy: Progressive supranuclear palsy and corticobasal degeneration","volume":"32","author":"Heckman","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1523\/JNEUROSCI.3642-15.2016","article-title":"G2019S-LRRK2 Expression Augments \u03b1-Synuclein Sequestration into Inclusions in Neurons","volume":"36","author":"Abdelmotilib","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.parkreldis.2017.06.004","article-title":"DCTN1-related neurodegeneration: Perry syndrome and beyond","volume":"41","author":"Konno","year":"2017","journal-title":"Park. Relat. Disord."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1001\/jamaneurol.2013.5100","article-title":"DCTN1Mutation Analysis in Families with Progressive Supranuclear Palsy\u2013Like Phenotypes","volume":"71","author":"Caroppo","year":"2014","journal-title":"JAMA Neurol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.parkreldis.2016.04.025","article-title":"DCTN1 p.K56R in progressive supranuclear palsy","volume":"28","author":"Gustavsson","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.parkreldis.2018.02.038","article-title":"DCTN1 F52L mutation case of Perry syndrome with progressive supranuclear palsy-like tauopathy","volume":"51","author":"Honda","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nrm2199","article-title":"Signal integration in the endoplasmic reticulum unfolded protein response","volume":"8","author":"Ron","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1042\/CS20220067","article-title":"The emerging role of LRRK2 in tauopathies","volume":"136","author":"Herbst","year":"2022","journal-title":"Clin. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:52:06Z","timestamp":1760122326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":108,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065281"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065281","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}