Lim SY, Klein C. Parkinson’s disease is predominantly a genetic disease. J Parkinsons Dis. 2024;14(3):467–82.
Article CAS PubMed PubMed Central Google Scholar
Cherian A, Puthenveedu KD, Vijayaraghavan A. Parkinson’s disease—genetic cause. Curr Opin Neurol. 2023;36(4):292–301.
Jia F, Fellner A, Kumar KR. Monogenic Parkinson’s disease: genotype, phenotype, pathophysiology, and genetic testing. Genes. 2022. https://doi.org/10.3390/genes13030471.
Article PubMed PubMed Central Google Scholar
Lange LM, Cerquera-Cleves C, Schipper M, Panagiotaropoulou G, Braun A, Kraft J, et al. Prioritizing Parkinson’s disease risk genes in genome-wide association loci. NPJ Parkinsons Dis. 2025;11(1):77.
Article PubMed PubMed Central Google Scholar
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388(6645):839–40.
Article CAS PubMed Google Scholar
Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276(5321):2045–7.
Article CAS PubMed Google Scholar
Bartels T, Ahlstrom LS, Leftin A, Kamp F, Haass C, Brown MF, et al. The N-terminus of the intrinsically disordered protein alpha-synuclein triggers membrane binding and helix folding. Biophys J. 2010;99(7):2116–24.
Article CAS PubMed PubMed Central Google Scholar
Vekrellis K, Emmanouilidou E, Xilouri M, Stefanis L. alpha-Synuclein in Parkinson’s disease: 12 years later. Cold Spring Harb Perspect Med. 2024;14(11):a041645.
Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S, et al. Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet. 2004;364(9440):1167–9.
Article CAS PubMed Google Scholar
Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, et al. alpha-Synuclein locus triplication causes Parkinson’s disease. Science. 2003;302(5646):841.
Article CAS PubMed Google Scholar
Pihlstrom L, Blauwendraat C, Cappelletti C, Berge-Seidl V, Langmyhr M, Henriksen SP, et al. A comprehensive analysis of SNCA-related genetic risk in sporadic Parkinson disease. Ann Neurol. 2018;84(1):117–29.
Article CAS PubMed PubMed Central Google Scholar
Fauvet B, Mbefo MK, Fares MB, Desobry C, Michael S, Ardah MT, et al. alpha-Synuclein in central nervous system and from erythrocytes, mammalian cells, and Escherichia coli exists predominantly as disordered monomer. J Biol Chem. 2012;287(19):15345–64.
Article CAS PubMed PubMed Central Google Scholar
Li JY, Englund E, Holton JL, Soulet D, Hagell P, Lees AJ, et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat Med. 2008;14(5):501–3.
Article CAS PubMed Google Scholar
Gima S, Oe K, Nishimura K, Ohgita T, Ito H, Kimura H, et al. Host-to-graft propagation of inoculated alpha-synuclein into transplanted human induced pluripotent stem cell-derived midbrain dopaminergic neurons. Regen Ther. 2024;25:229–37.
Article CAS PubMed PubMed Central Google Scholar
Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ, et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012;338(6109):949–53.
Article CAS PubMed PubMed Central Google Scholar
Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211.
Zampar S, Di Gregorio SE, Grimmer G, Watts JC, Ingelsson M. “Prion-like” seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders. Front Neurosci. 2024;18:1436262.
Article PubMed PubMed Central Google Scholar
Cummings J, Osse AML, Cammann D, Powell J, Chen J. Anti-amyloid monoclonal antibodies for the treatment of Alzheimer’s disease. BioDrugs. 2024;38(1):5–22.
Article CAS PubMed Google Scholar
Alfaidi M, Barker RA, Kuan WL. An update on immune-based alpha-synuclein trials in Parkinson’s disease. J Neurol. 2024;272(1):21.
Article PubMed PubMed Central Google Scholar
Schenk DB, Koller M, Ness DK, Griffith SG, Grundman M, Zago W, et al. First-in-human assessment of PRX002, an anti-alpha-synuclein monoclonal antibody, in healthy volunteers. Mov Disord. 2017;32(2):211–8.
Article CAS PubMed Google Scholar
Schofield DJ, Irving L, Calo L, Bogstedt A, Rees G, Nuccitelli A, et al. Preclinical development of a high affinity alpha-synuclein antibody, MEDI1341, that can enter the brain, sequester extracellular alpha-synuclein and attenuate alpha-synuclein spreading in vivo. Neurobiol Dis. 2019;132:104582.
Article CAS PubMed Google Scholar
Fjord-Larsen L, Thougaard A, Wegener KM, Christiansen J, Larsen F, Schroder-Hansen LM, et al. Nonclinical safety evaluation, pharmacokinetics, and target engagement of Lu AF82422, a monoclonal IgG1 antibody against alpha-synuclein in development for treatment of synucleinopathies. MAbs. 2021;13(1):1994690.
Article PubMed PubMed Central Google Scholar
Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, et al. Development of an aggregate-selective, human-derived alpha-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson’s disease models. Neurobiol Dis. 2019;124:276–88.
Article CAS PubMed Google Scholar
Nordstrom E, Eriksson F, Sigvardson J, Johannesson M, Kasrayan A, Jones-Kostalla M, et al. ABBV-0805, a novel antibody selective for soluble aggregated alpha-synuclein, prolongs lifespan and prevents buildup of alpha-synuclein pathology in mouse models of Parkinson’s disease. Neurobiol Dis. 2021;161:105543.
Pagano G, Taylor KI, Anzures-Cabrera J, Marchesi M, Simuni T, Marek K, et al. Trial of prasinezumab in early-stage Parkinson’s disease. N Engl J Med. 2022;387(5):421–32.
Article CAS PubMed Google Scholar
Lang AE, Siderowf AD, Macklin EA, Poewe W, Brooks DJ, Fernandez HH, et al. Trial of cinpanemab in early Parkinson’s disease. N Engl J Med. 2022;387(5):408–20.
Article CAS PubMed Google Scholar
Pagano G, Taylor KI, Anzures Cabrera J, Simuni T, Marek K, Postuma RB, et al. Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease. Nat Med. 2024;30(4):1096–103.
Article CAS PubMed PubMed Central Google Scholar
Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, et al. Discriminating alpha-synuclein strains in Parkinson’s disease and multiple system atrophy. Nature. 2020;578(7794):273–7.
Article CAS PubMed PubMed Central Google Scholar
Heneka MT, Morgan D, Jessen F. Passive anti-amyloid beta immunotherapy in Alzheimer’s disease-opportunities and challenges. Lancet. 2024;404(10468):2198–208.
Article CAS PubMed Google Scholar
McFarthing K, Buff S, Rafaloff G, Pitzer K, Fiske B, Navangul A, et al. Parkinson’s disease drug therapies in the clinical trial pipeline: 2024 update. J Parkinsons Dis. 2024;14(5):899–912.
Comments (0)