RXR nuclear receptor signaling modulates lipid metabolism and triggers lysosomal clearance of alpha-synuclein in neuronal models of synucleinopathy

Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840

Article  CAS  PubMed  Google Scholar 

Parkinson’s Foundation. https://www.parkinson.org/understanding-parkinsons/statistics Accessed 23 September 2023.

Parkinson J (2002) An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 14(2):223–36; discussion 222.

Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D et al (2019) Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol 18(12):1091–1102

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brockmann K, Schulte C, Hauser AK, Lichtner P, Huber H, Maetzler W et al (2013) SNCA: major genetic modifier of age at onset of Parkinson’s disease. Mov Disord Off J Mov Disord Soc 28(9):1217–1221

Article  CAS  Google Scholar 

Edwards TL, Scott WK, Almonte C, Burt A, Powell EH, Beecham GW et al (2010) Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease. Ann Hum Genet 74(2):97–109

Article  CAS  PubMed  PubMed Central  Google Scholar 

Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276(5321):2045–2047

Article  CAS  PubMed  Google Scholar 

Krüger R, Kuhn W, Müller T, Woitalla D, Graeber M, Kösel S et al (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet 18(2):106–108

Article  PubMed  Google Scholar 

Zarranz JJ, Alegre J, Gómez-Esteban JC, Lezcano E, Ros R, Ampuero I et al (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 55(2):164–173

Article  CAS  PubMed  Google Scholar 

Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, Sherman H, Yu I, Shah B, et al (2013) Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson’s disease. Mov Disord Off J Mov Disord Soc 28(6):811–813

Lesage S, Anheim M, Letournel F, Bousset L, Honoré A, Rozas N et al (2013) G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol 73(4):459–471

Article  CAS  PubMed  Google Scholar 

Kiely AP, Ling H, Asi YT, Kara E, Proukakis C, Schapira AH et al (2015) Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation. Mol Neurodegener 10:41

Article  PubMed  PubMed Central  Google Scholar 

Pasanen P, Myllykangas L, Siitonen M, Raunio A, Kaakkola S, Lyytinen J et al (2014) Novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson’s disease-type pathology. Neurobiol Aging 35(9):2180.e1–5

Article  CAS  PubMed  Google Scholar 

Yoshino H, Hirano M, Stoessl AJ, Imamichi Y, Ikeda A, Li Y, et al (2017) Homozygous alpha-synuclein p.A53V in familial Parkinson’s disease. Neurobiol Aging 57:248.e7–248.e12.

Liu H, Koros C, Strohäker T, Schulte C, Bozi M, Varvaresos S et al (2021) A novel SNCA A30G mutation causes familial Parkinson’s disease. Mov Disord Off J Mov Disord Soc 36(7):1624–1633

Article  CAS  Google Scholar 

Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J et al (2003) Alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302(5646):841

Article  CAS  PubMed  Google Scholar 

Byers B, Cord B, Nguyen HN, Schüle B, Fenno L, Lee PC et al (2011) SNCA triplication Parkinson’s patient’s iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress. PLoS One 6(11):e26159

Article  PubMed  PubMed Central  Google Scholar 

Devine MJ, Ryten M, Vodicka P, Thomson AJ, Burdon T, Houlden H et al (2011) Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus. Nat Commun 2:440

Article  PubMed  Google Scholar 

Chartier-Harlin MC, Kachergus J, Roumier C, Mouroux V, Douay X, Lincoln S et al (2004) Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet Lond Engl 364(9440):1167–1169

Article  CAS  Google Scholar 

Konno T, Ross OA, Puschmann A, Dickson DW, Wszolek ZK (2016) Autosomal dominant Parkinson’s disease caused by SNCA duplications. Parkinsonism Relat Disord 22(Suppl 1):S1–S6

Laperle AH, Sances S, Yucer N, Dardov VJ, Garcia VJ, Ho R et al (2020) iPSC modeling of young-onset Parkinson’s disease reveals a molecular signature of disease and novel therapeutic candidates. Nat Med 26(2):289–299

Article  CAS  PubMed  Google Scholar 

Wong YC, Krainc D (2017) α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat Med 23(2):1–13

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stefanis L (2012) α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med 2(2):a009399

Article  PubMed  PubMed Central  Google Scholar 

Tripathi A, Fanning S, Dettmer U (2021) Lipotoxicity downstream of α-synuclein imbalance: a relevant pathomechanism in synucleinopathies? Biomolecules 12(1):40

Article  PubMed  PubMed Central  Google Scholar 

Flores-Leon M, Outeiro TF (2023) More than meets the eye in Parkinson’s disease and other synucleinopathies: from proteinopathy to lipidopathy. Acta Neuropathol (Berl) 146(3):369–385

Article  CAS  PubMed  Google Scholar 

Fanning S, Selkoe D, Dettmer U (2020) Parkinson’s disease: proteinopathy or lipidopathy? NPJ Park Dis 6:3

Article  CAS  Google Scholar 

Shahmoradian SH, Lewis AJ, Genoud C, Hench J, Moors TE, Navarro PP et al (2019) Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nat Neurosci 22(7):1099–1109

Article  CAS  PubMed  Google Scholar 

Gai WP, Yuan HX, Li XQ, Power JT, Blumbergs PC, Jensen PH (2000) In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies. Exp Neurol 166(2):324–333

Article  CAS  PubMed  Google Scholar 

Araki K, Yagi N, Ikemoto Y, Yagi H, Choong CJ, Hayakawa H et al (2015) Synchrotron FTIR micro-spectroscopy for structural analysis of Lewy bodies in the brain of Parkinson’s disease patients. Sci Rep 5:17625

Article  CAS  PubMed  PubMed Central  Google Scholar 

Moors TE, Maat CA, Niedieker D, Mona D, Petersen D, Timmermans-Huisman E et al (2021) The subcellular arrangement of alpha-synuclein proteoforms in the Parkinson’s disease brain as revealed by multicolor STED microscopy. Acta Neuropathol (Berl) 142(3):423–448

Article  CAS  PubMed  Google Scholar 

Bodner CR, Dobson CM, Bax A (2009) Multiple tight phospholipid-binding modes of alpha-synuclein revealed by solution NMR spectroscopy. J Mol Biol. 390(4):775–90

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bodner CR, Maltsev AS, Dobson CM, Bax A (2010) Differential phospholipid binding of alpha-synuclein variants implicated in Parkinson’s disease revealed by solution NMR spectroscopy. Biochemistry 49(5):862–871

Article  CAS  PubMed  Google Scholar 

Ruipérez V, Darios F, Davletov B (2010) Alpha-synuclein, lipids and Parkinson’s disease. Prog Lipid Res 49(4):420–428

Article  PubMed  Google Scholar 

Stöckl M, Fischer P, Wanker E, Herrmann A (2008) Alpha-synuclein selectively binds to anionic phospholipids embedded in liquid-disordered domains. J Mol Biol 375(5):1394–1404

Article  PubMed  Google Scholar 

Sharon R, Goldberg MS, Bar-Josef I, Betensky RA, Shen J, Selkoe DJ (2001) alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc Natl Acad Sci USA 98(16):9110–9115

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