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Research Articles

Wild-type GBA1 increases the α-synuclein tetramer-monomer ratio, reduces lipid-rich aggregates, and attenuates motor and cognitive deficits in mice. Glajch KE, Moors TE, Chen Y, Bechade PA, Nam AY, Rajsombath MM, McCaffery TD, Dettmer U, Weihofen A, Hirst WD, Selkoe DJ, Nuber S.Proc Natl Acad Sci U S A. 2021 Aug 3;118(31):e2103425118. doi: 10.1073/pnas.2103425118.

Excess membrane binding of monomeric alpha-, beta- and gamma-synuclein is invariably associated with inclusion formation and toxicity. Kim TE, Newman AJ, Imberdis T, Brontesi L, Tripathi A, Ramalingam N, Fanning S, Selkoe D, Dettmer U. Hum Mol Genet. 2021 Nov 16;30(23):2332-2346. doi: 10.1093/hmg/ddab188.

Crowded organelles, lipid accumulation, and abnormal membrane tubulation in cellular models of enhanced α-synuclein membrane interaction. Ericsson M, von Saucken V, Newman AJ, Doehr L, Hoesch C, Kim TE, Dettmer U. Brain Res. 2021 May 1;1758:147349. doi: 10.1016/j.brainres.2021.147349.

Temperature is a key determinant of alpha- and beta-synuclein membrane interactions in neurons. Ramalingam N, Dettmer U. J Biol Chem. 2021 Jan 8;296:100271. doi: 10.1016/j.jbc.2021.100271.

Upregulation of Cellular Palmitoylation Mitigates α-Synuclein Accumulation and Neurotoxicity. Ho GPH, Ramalingam N, Imberdis T, Wilkie EC, Dettmer U, Selkoe DJ. Mov Disord. 2021 Feb;36(2):348-359. doi: 10.1002/mds.28346.

A Stearoyl-Coenzyme A Desaturase Inhibitor Prevents Multiple Parkinson Disease Phenotypes in α-Synuclein Mice. Nuber S, Nam AY, Rajsombath MM, Cirka H, Hronowski X, Wang J, Hodgetts K, Kalinichenko LS, Müller CP, Lambrecht V, Winkler J, Weihofen A, Imberdis T, Dettmer U, Fanning S, Selkoe DJ. Ann Neurol. 2021 Jan;89(1):74-90. doi: 10.1002/ana.25920.

Rapid Alpha-Synuclein Toxicity in a Neural Cell Model and Its Rescue by a Stearoyl-CoA Desaturase Inhibitor. Terry-Kantor E, Tripathi A, Imberdis T, LaVoie ZM, Ho GPH, Selkoe D, Fanning S, Ramalingam N, Dettmer U. Int J Mol Sci. 2020 Jul 22;21(15):5193. doi: 10.3390/ijms21155193.

Cell models of lipid-rich α-synuclein aggregation validate known modifiers of α-synuclein biology and identify stearoyl-CoA desaturase. Imberdis T, Negri J, Ramalingam N, Terry-Kantor E, Ho G, Fanning S, Stirtz G, Levy O, Young-Pearse T, Selkoe D, Dettmer U. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20760-20769.  doi: 10.1073/pnas.1903216116.

Lipidomic Analysis of α-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment. Fanning S, Haque A, Imberdis T, Baru V, Barrasa MI, Nuber S, Termine D, Ramalingam N, Ho GPH, Noble T, Sandoe J, Lou Y, Landgraf D, Freyzon Y, Newby G, Soldner F, Terry-Kantor E, Kim TE, Hofbauer HF, Becuwe M, Jaenisch R, Pincus D, Clish CB, Walther TC, Farese RV Jr, Srinivasan S, Welte MA, Kohlwein SD, Dettmer U*, Lindquist S, Selkoe D*.  Mol Cell. 2019 Mar 7;73(5):1001-1014.e8. doi: 10.1016/j.molcel.2018.11.028. (* corresponding authors)

Studying α-Synuclein Conformation by Intact-Cell Cross-Linking. Imberdis T, Fanning S, Newman A, Ramalingam N, Dettmer U*. Methods Mol Biol. 2019;1948:77-91. doi: 10.1007/978-1-4939-9124-2_8.

Abrogating Native α-Synuclein Tetramers in Mice Causes a L-DOPA-Responsive Motor Syndrome Closely Resembling Parkinson’s Disease. Nuber S, Rajsombath M, Minakaki G, Winkler J, Müller CP, Ericsson M, Caldarone B, Dettmer U, Selkoe DJ. Neuron. 2018 Oct 10;100(1):75-90.e5. doi: 10.1016/j.neuron.2018.09.014.

Nortriptyline inhibits aggregation and neurotoxicity of alpha-synuclein by enhancing reconfiguration of the monomeric form. Collier TJ, Srivastava KR, Justman C, Grammatopoulous T, Hutter-Paier B, Prokesch M, Havas D, Rochet JC, Liu F, Jock K, de Oliveira P, Stirtz GL, Dettmer U, Sortwell CE, Feany MB, Lansbury P, Lapidus L, Paumier KL. Neurobiol Dis. 2017 Oct;106:191-204. doi: 10.1016/j.nbd.2017.07.007.

Loss of native α-synuclein multimerization by strategically mutating its amphipathic helix causes abnormal vesicle interactions in neuronal cells. Dettmer U*, Ramalingam N, von Saucken VE, Kim TE, Newman AJ, Terry-Kantor E, Nuber S, Ericsson M, Fanning S, Bartels T, Lindquist S, Levy OA, Selkoe D. Hum Mol Genet. 2017 Sep 15;26(18):3466-3481. doi: 10.1093/hmg/ddx227. (* corresponding author)

KTKEGV repeat motifs are key mediators of normal α-synuclein tetramerization: Their mutation causes excess monomers and neurotoxicity. Dettmer U, Newman AJ, von Saucken VE Bartels T, Selkoe D. Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9596-601. doi: 10.1073/pnas.1505953112.

Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation. Dettmer U, Newman AJ, Soldner F, Luth ES, Kim NC, von Saucken VE, Sanderson JB, Jaenisch R, Bartels T, Selkoe D. Nat Commun. 2015 Jun 16;6:7314. doi: 10.1038/ncomms8314.

Purification of α-synuclein from human brain reveals an instability of endogenous multimers as the protein approaches purity. Luth ES, Bartels T, Dettmer U, Kim NC, Selkoe D. Biochemistry. 2015 Jan 20;54(2):279-92. doi: 10.1021/bi501188a.

A New Method for Quantitative Immunoblotting of Endogenous α-Synuclein. Newman AJ, Selkoe D, Dettmer U: PLoS One. 2013 Nov 20;8(11):e81314. doi: 10.1371/journal.pone.0081314

In vivo cross-linking reveals principally oligomeric forms of α-synuclein and β-synuclein in neurons and non-neural cells. Dettmer U, Newman AJ, Luth ES, Bartels T, Selkoe D: J Biol Chem. 2013 Mar 1;288(9):6371-85. doi: 10.1074/jbc.M112.403311.

The Transmembrane Protein 147 (TMEM147) is a Component of the Nicalin-NOMO Protein Complex. Dettmer U, Kuhn PH, Abou-Ajram C, Lichtenthaler SF, Krüger M, Kremmer E, Haass C, Haffner C. J Biol Chem. 2010 Aug 20;285(34):26174-81. doi: 10.1074/jbc.M110.132548.

The Nicastrin-like protein Nicalin regulates assembly and stability of the Nicalin-nodal modulator (NOMO) membrane protein complex. Haffner C, Dettmer U, Weiler T, Haass C. J Biol Chem. 2007 Apr 6;282(14):10632-8.

 

 

Reviews/Commentaries

Vesicle trafficking and lipid metabolism in synucleinopathy. Fanning S, Selkoe D, Dettmer U. Acta Neuropathol. 2021 Apr;141(4):491-510. doi: 10.1007/s00401-020-02177-z. Epub 2020 Jun 30.PMID: 32607605 Review.

Soluble endogenous oligomeric α-synuclein species in neurodegenerative diseases: Expression, spreading, and cross-talk. Kayed R, Dettmer U, Lesné SE. J Parkinsons Dis. 2020;10(3):791-818. doi: 10.3233/JPD-201965.PMID: 32508330 Free PMC article. Review.

Parkinson’s disease: proteinopathy or lipidopathy? Fanning S, Selkoe D, Dettmer U. NPJ Parkinsons Dis. 2020 Jan 3;6:3. doi: 10.1038/s41531-019-0103-7. eCollection 2020.PMID: 31909184 Free PMC article. Review.

Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration. Yeboah F, Kim TE, Bill A, Dettmer U. Neurobiol Dis. 2019 Jul 24;132:104543. doi: 10.1016/j.nbd.2019.104543. [Epub ahead of print] Review.

Rationally Designed Variants of α-Synuclein Illuminate Its in vivo Structural Properties in Health and Disease. Dettmer U. Front Neurosci. 2018 Sep 25;12:623. doi: 10.3389/fnins.2018.00623. eCollection 2018. Review.

New insights into cellular α-synuclein homeostasis in health and disease. Dettmer U, Selkoe D, Bartels T. Curr Opin Neurobiol. 2016 Feb;36:15-22. doi: 10.1016/j.conb.2015.07.007

ExPLAining early synucleinopathies. Dettmer U, Bartels T. Brain. 2015 Jun;138(Pt 6):1449-51. doi: 10.1093/brain/awv099

Defining the native state of α-synuclein. Selkoe D, Dettmer U, Luth E, Kim N, Newman AJ, Bartels T. Neurodegener Diseases. 2013 Oct 30; 13(2-3):114-7. doi: 10.1159/000355516.

 

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