Acta Neuropathologica

, Volume 138, Issue 6, pp 971–986 | Cite as

Early defects in translation elongation factor 1α levels at excitatory synapses in α-synucleinopathy

  • Sonja Blumenstock
  • Maria Florencia Angelo
  • Finn Peters
  • Mario M. Dorostkar
  • Viktoria C. Ruf
  • Manja Luckner
  • Sophie Crux
  • Lenka Slapakova
  • Thomas Arzberger
  • Stéphane Claverol
  • Etienne HerzogEmail author
  • Jochen HermsEmail author
Original Paper


Cognitive decline and dementia in neurodegenerative diseases are associated with synapse dysfunction and loss, which may precede neuron loss by several years. While misfolded and aggregated α-synuclein is recognized in the disease progression of synucleinopathies, the nature of glutamatergic synapse dysfunction and loss remains incompletely understood. Using fluorescence-activated synaptosome sorting (FASS), we enriched excitatory glutamatergic synaptosomes from mice overexpressing human alpha-synuclein (h-αS) and wild-type littermates to unprecedented purity. Subsequent label-free proteomic quantification revealed a set of proteins differentially expressed upon human alpha-synuclein overexpression. These include overrepresented proteins involved in the synaptic vesicle cycle, ER–Golgi trafficking, metabolism and cytoskeleton. Unexpectedly, we found and validated a steep reduction of eukaryotic translation elongation factor 1 alpha (eEF1A1) levels in excitatory synapses at early stages of h-αS mouse model pathology. While eEF1A1 reduction correlated with the loss of postsynapses, its immunoreactivity was found on both sides of excitatory synapses. Moreover, we observed a reduction in eEF1A1 immunoreactivity in the cingulate gyrus neuropil of patients with Lewy body disease along with a reduction in PSD95 levels. Altogether, our results suggest a link between structural impairments underlying cognitive decline in neurodegenerative disorders and local synaptic defects. eEF1A1 may therefore represent a limiting factor to synapse maintenance.


Alpha-synuclein Elongation factor 1 alpha Synapse Proteomics Lewy body dementia FASS 



We thank Sarah Hanselka, Katharina Bayer, Michael Schmidt, Dr. Christelle Martin, Melissa Deshors, Dr. Norbert Buresch (Neurobiobank Munich), Dr. Vincent Pitard (Flow cytometry facility, CNRS UMS 3427, INSERM US 005, Univ. Bordeaux), Patrice Mascalchi (Bordeaux Imaging Center, CNRS, INSERM, Univ. Bordeaux) and the Biochemistry and biophysics facility of Bordeaux Neurocampus (CNRS, INSERM, Univ. Bordeaux) for their excellent technical support and animal care. We are also thankful towards Stephan Müller for his expertise in proteomics and advice on our data.

Author contributions

SB performed design of the experiment, subcellular fractioning, FASS sorting, validation of results in mouse and human tissue, bioinformatics and interpretation of results and wrote the manuscript. MFA provided expertise and performed subcellular fractioning, FASS sorting and Western blotting with SB. FP performed programming for image analysis. MMD performed bioinformatic analyses. MMD, VCR and TA selected human tissue and provided neuropathological expertise. ML performed EM experiments and EM data analysis. SCl performed mass spectrometry and analysis of the MS raw data. EH performed STED microscopy. SCr and LS provided technical support. VCR, MMD, MFA, EH and JH helped with manuscript preparation. EH and JH supervised the study, contributed to conception, design and manuscript writing and provided financial support and final approval of the manuscript.


This work was funded by the Munich Cluster for Systems Neurology SyNergy (EXC1010) to SB, SC and JH; the German Academic Exchange Service (DAAD) to SB; the French Agence Nationale de la Recherche (ANR-12-JSV4-0005-01VGLUT-IQ and ANR-10-LABX-43 BRAIN) to EH; the Fondation pour la Recherche Médicale (ING20150532192) to EH and the CNRS PICS program to EH.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

401_2019_2063_MOESM1_ESM.xlsx (50 kb)
Supplementary file1 (XLSX 50 kb)
401_2019_2063_MOESM2_ESM.docx (3.6 mb)
Supplementary file2 (DOCX 3644 kb)


  1. 1.
    Abbas W, Kumar A, Herbein G (2015) The eEF1A proteins: at the crossroads of oncogenesis, apoptosis, and viral infections. Front Oncol 5:75. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Amschl D, Neddens J, Havas D, Flunkert S, Rabl R, Römer H, Rockenstein E, Masliah E, Windisch M, Hutter-Paier B (2013) Time course and progression of wild type α-Synuclein accumulation in a transgenic mouse model. BMC Neurosci 14:1CrossRefGoogle Scholar
  3. 3.
    Beckelman BC, Day S, Zhou X, Donohue M, Gouras GK, Klann E, Keene CD, Ma T (2016) Dysregulation of elongation factor 1A expression is correlated with synaptic plasticity impairments in Alzheimer’s disease. J Alzheimers Dis JAD 54:669–678. CrossRefGoogle Scholar
  4. 4.
    Bellucci A, Zaltieri M, Navarria L, Grigoletto J, Missale C, Spano P (2012) From α-synuclein to synaptic dysfunctions: new insights into the pathophysiology of Parkinson’s disease. Brain Res 1476:183–202. CrossRefGoogle Scholar
  5. 5.
    Ben Gedalya T, Loeb V, Israeli E, Altschuler Y, Selkoe DJ, Sharon R (2009) α-Synuclein and polyunsaturated fatty acids promote clathrin-mediated endocytosis and synaptic vesicle recycling. Traffic 10:218–234. CrossRefGoogle Scholar
  6. 6.
    Bendor JT, Logan TP, Edwards RH (2013) The function of α-synuclein. Neuron 79:1044–1066. CrossRefGoogle Scholar
  7. 7.
    Biesemann C, Grønborg M, Luquet E, Wichert SP, Bernard V, Bungers SR, Cooper B, Varoqueaux F, Li L, Byrne JA, Urlaub H, Jahn O, Brose N, Herzog E (2014) Proteomic screening of glutamatergic mouse brain synaptosomes isolated by fluorescence activated sorting. EMBO J 33:157–170. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Blumenstock S, Rodrigues EF, Peters F, Blazquez-Llorca L, Schmidt F, Giese A, Herms J (2017) Seeding and transgenic overexpression of alpha-synuclein triggers dendritic spine pathology in the neocortex. EMBO Mol Med 9:716–731. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Braak H, Del Tredici K, Rüb U, de Vos RA, Steur ENJ, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211CrossRefPubMedGoogle Scholar
  10. 10.
    Bunai F, Ando K, Ueno H, Numata O (2006) Tetrahymena eukaryotic translation elongation factor 1A (eEF1A) bundles filamentous actin through dimer formation. J Biochem (Tokyo) 140:393–399. CrossRefGoogle Scholar
  11. 11.
    Calì T, Ottolini D, Negro A, Brini M (2012) α-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum–mitochondria interactions. J Biol Chem 287:17914–17929. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Calo L, Wegrzynowicz M, Santivañez-Perez J, Grazia Spillantini M (2016) Synaptic failure and α-synuclein. Mov Disord 31:169–177. CrossRefGoogle Scholar
  13. 13.
    Caraveo G, Auluck PK, Whitesell L, Chung CY, Baru V, Mosharov EV, Yan X, Ben-Johny M, Soste M, Picotti P, Kim H, Caldwell KA, Caldwell GA, Sulzer D, Yue DT, Lindquist S (2014) Calcineurin determines toxic versus beneficial responses to -synuclein. Proc Natl Acad Sci 111:E3544–E3552. CrossRefGoogle Scholar
  14. 14.
    Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, Guertin DA, Chang JH, Lindquist RA, Moffat J, Golland P, Sabatini DM (2006) Cell Profiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 7:R100. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cartelli D, Aliverti A, Barbiroli A, Santambrogio C, Ragg EM, Casagrande FVM, Cantele F, Beltramone S, Marangon J, De Gregorio C, Pandini V, Emanuele M, Chieregatti E, Pieraccini S, Holmqvist S, Bubacco L, Roybon L, Pezzoli G, Grandori R, Arnal I, Cappelletti G (2016) α-Synuclein is a novel microtubule dynamase. Sci Rep 6:33289. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chai YJ, Sierecki E, Tomatis VM, Gormal RS, Giles N, Morrow IC, Xia D, Götz J, Parton RG, Collins BM, Gambin Y, Meunier FA (2016) Munc18-1 is a molecular chaperone for α-synuclein, controlling its self-replicating aggregation. J Cell Biol 214:705–718. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Cho S-J, Jung J-S, Ko BH, Jin I, Moon IS (2004) Presence of translation elongation factor-1A (eEF1A) in the excitatory postsynaptic density of rat cerebral cortex. Neurosci Lett 366:29–33. CrossRefGoogle Scholar
  18. 18.
    Cho S-J, Lee H-S, Dutta S, Seog D-H, Moon I-S (2012) Translation elongation factor-1A1 (eEF1A1) localizes to the spine by domain III. BMB Rep 45:227–232. CrossRefGoogle Scholar
  19. 19.
    Chuang S-M, Chen L, Lambertson D, Anand M, Kinzy TG, Madura K (2005) Proteasome-mediated degradation of cotranslationally damaged proteins involves translation elongation factor 1A. Mol Cell Biol 25:403–413. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cohen LD, Zuchman R, Sorokina O, Müller A, Dieterich DC, Armstrong JD, Ziv T, Ziv NE (2013) Metabolic turnover of synaptic proteins: kinetics, interdependencies and implications for synaptic maintenance. PLoS ONE 8:e63191. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    De Robertis E, De Lores Rodriguez, Arnaiz G, Pellegrino De Iraldi A (1962) Isolation of synaptic vesicles from nerve endings of the rat brain. Nature 194:794–795CrossRefGoogle Scholar
  22. 22.
    Delaidelli A, Jan A, Herms J, Sorensen PH (2019) Translational control in brain pathologies: biological significance and therapeutic opportunities. Acta Neuropathol (Berl) 137:535–555. CrossRefGoogle Scholar
  23. 23.
    Di Sano F, Piacentini M (2012) Reticulon protein-1C: a new hope in the treatment of different neuronal diseases. Int J Cell Biol 2012:1–9. CrossRefGoogle Scholar
  24. 24.
    Diao J, Burré J, Vivona S, Cipriano DJ, Sharma M, Kyoung M, Südhof TC, Brunger AT (2013) Native α-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2. eLife. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P (1995) Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging 16:285–298. CrossRefGoogle Scholar
  26. 26.
    Dieterich DC, Kreutz MR (2016) Proteomics of the synapse—a quantitative approach to neuronal plasticity. Mol Cell Proteom MCP 15:368–381. CrossRefGoogle Scholar
  27. 27.
    Emanuele M, Esposito A, Camerini S, Antonucci F, Ferrara S, Seghezza S, Catelani T, Crescenzi M, Marotta R, Canale C, Matteoli M, Menna E, Chieregatti E (2016) Exogenous alpha-synuclein alters pre- and post-synaptic activity by fragmenting lipid rafts. EBioMedicine 7:191–204. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fernández E, Collins MO, Uren RT, Kopanitsa MV, Komiyama NH, Croning MDR, Zografos L, Armstrong JD, Choudhary JS, Grant SGN (2009) Targeted tandem affinity purification of PSD-95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins. Mol Syst Biol 5:269. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Fortin DL (2004) Lipid rafts mediate the synaptic localization of α-synuclein. J Neurosci 24:6715–6723. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Fujimura M, Usuki F, Cheng J, Zhao W (2016) Prenatal low-dose methylmercury exposure impairs neurite outgrowth and synaptic protein expression and suppresses TrkA pathway activity and eEF1A1 expression in the rat cerebellum. Toxicol Appl Pharmacol 298:1–8. CrossRefGoogle Scholar
  31. 31.
    Fusco G, Pape T, Stephens AD, Mahou P, Costa AR, Kaminski CF, Kaminski Schierle GS, Vendruscolo M, Veglia G, Dobson CM, De Simone A (2016) Structural basis of synaptic vesicle assembly promoted by α-synuclein. Nat Commun 7:12563. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Garcia-Esparcia P, Hernández-Ortega K, Koneti A, Gil L, Delgado-Morales R, Castaño E, Carmona M, Ferrer I (2015) Altered machinery of protein synthesis is region- and stage-dependent and is associated with α-synuclein oligomers in Parkinson’s disease. Acta Neuropathol Commun 3:76. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Giustetto M, Hegde AN, Si K, Casadio A, Inokuchi K, Pei W, Kandel ER, Schwartz JH (2003) Axonal transport of eukaryotic translation elongation factor 1α mRNA couples transcription in the nucleus to long-term facilitation at the synapse. Proc Natl Acad Sci 100:13680–13685CrossRefPubMedGoogle Scholar
  34. 34.
    Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–88PubMedPubMedCentralGoogle Scholar
  35. 35.
    Gross SR, Kinzy TG (2005) Translation elongation factor 1A is essential for regulation of the actin cytoskeleton and cell morphology. Nat Struct Mol Biol 12:772–778. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Guardia-Laguarta C, Area-Gomez E, Rub C, Liu Y, Magrane J, Becker D, Voos W, Schon EA, Przedborski S (2014) α-Synuclein is localized to mitochondria-associated ER membranes. J Neurosci 34:249–259. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hafner A-S, Donlin-Asp PG, Leitch B, Herzog E, Schuman EM (2019) Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments. Science. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Hashimoto K, Ishima T (2011) Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol. PLoS ONE 6:e17431. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Herzog E, Nadrigny F, Silm K, Biesemann C, Helling I, Bersot T, Steffens H, Schwartzmann R, Nagerl UV, El Mestikawy S, Rhee J, Kirchhoff F, Brose N (2011) In vivo imaging of intersynaptic vesicle exchange using VGLUT1Venus knock-in mice. J Neurosci 31:15544–15559. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hosp F, Mann M (2017) A primer on concepts and applications of proteomics in neuroscience. Neuron 96:558–571. CrossRefGoogle Scholar
  41. 41.
    Hu Q, Wang G (2016) Mitochondrial dysfunction in Parkinson’s disease. Transl Neurodegener 5:14. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Huang DW, Sherman BT, Lempicki RA (2008) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4:44–57. CrossRefGoogle Scholar
  43. 43.
    Huang DW, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37:1–13. CrossRefGoogle Scholar
  44. 44.
    Iketani M, Iizuka A, Sengoku K, Kurihara Y, Nakamura F, Sasaki Y, Sato Y, Yamane M, Matsushita M, Nairn AC, Takamatsu K, Goshima Y, Takei K (2013) Regulation of neurite outgrowth mediated by localized phosphorylation of protein translational factor eEF2 in growth cones. Dev Neurobiol 73:230–246. CrossRefGoogle Scholar
  45. 45.
    Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2012) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. Osteoarthr Cartil 20:256–260CrossRefGoogle Scholar
  46. 46.
    Liu G, Tang J, Edmonds BT, Murray J, Levin S, Condeelis J (1996) F-actin sequesters elongation factor 1alpha from interaction with aminoacyl-tRNA in a pH-dependent reaction. J Cell Biol 135:953–963CrossRefGoogle Scholar
  47. 47.
    Liu G, Wang P, Li X, Li Y, Xu S, Uéda K, Chan P, Yu S (2013) Alpha-synuclein promotes early neurite outgrowth in cultured primary neurons. J Neural Transm 120:1331–1343. CrossRefGoogle Scholar
  48. 48.
    Logan T, Bendor J, Toupin C, Thorn K, Edwards RH (2017) α-Synuclein promotes dilation of the exocytotic fusion pore. Nat Neurosci 20:681–689. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Lotharius J, Brundin P (2002) Pathogenesis of Parkinson’s disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci 3:932–942. CrossRefGoogle Scholar
  50. 50.
    Luquet E, Biesemann C, Munier A, Herzog E (2017) Purification of synaptosome populations using fluorescence-activated synaptosome sorting. Methods Mol Biol Clifton NJ 1538:121–134. CrossRefGoogle Scholar
  51. 51.
    Ma T, Trinh MA, Wexler AJ, Bourbon C, Gatti E, Pierre P, Cavener DR, Klann E (2013) Suppression of eIF2α kinases alleviates Alzheimer’s disease-related plasticity and memory deficits. Nat Neurosci 16:1299–1305. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Masliah E (2000) Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 287:1265–1269. CrossRefGoogle Scholar
  53. 53.
    Mateyak MK, Kinzy TG (2010) eEF1A: thinking outside the ribosome. J Biol Chem 285:21209–21213. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    McClatchy DB, Fang G, Levey AI (2006) Elongation factor 1A family regulates the recycling of the M4 muscarinic acetylcholine receptor. Neurochem Res 31:975–988. CrossRefGoogle Scholar
  55. 55.
    McInnes J, Wierda K, Snellinx A, Bounti L, Wang Y-C, Stancu I-C, Apóstolo N, Gevaert K, Dewachter I, Spires-Jones TL, De Strooper B, De Wit J, Zhou L, Verstreken P (2018) Synaptogyrin-3 mediates presynaptic dysfunction induced by Tau. Neuron 97:823–835.e8. CrossRefGoogle Scholar
  56. 56.
    Moreno JA, Radford H, Peretti D, Steinert JR, Verity N, Martin MG, Halliday M, Morgan J, Dinsdale D, Ortori CA, Barrett DA, Tsaytler P, Bertolotti A, Willis AE, Bushell M, Mallucci GR (2012) Sustained translational repression by eIF2α-P mediates prion neurodegeneration. Nature 485:507–511. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Nakamura K, Nemani VM, Azarbal F, Skibinski G, Levy JM, Egami K, Munishkina L, Zhang J, Gardner B, Wakabayashi J, Sesaki H, Cheng Y, Finkbeiner S, Nussbaum RL, Masliah E, Edwards RH (2011) Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. J Biol Chem 286:20710–20726. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Nakayama K, Suzuki Y, Yazawa I (2012) Binding of neuronal α-synuclein to β-III tubulin and accumulation in a model of multiple system atrophy. Biochem Biophys Res Commun 417:1170–1175. CrossRefGoogle Scholar
  59. 59.
    Nemani VM, Lu W, Berge V, Nakamura K, Onoa B, Lee MK, Chaudhry FA, Nicoll RA, Edwards RH (2010) Increased expression of α-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis. Neuron 65:66–79. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Park J, Park Y, Ryu I, Choi M-H, Lee HJ, Oh N, Kim K, Kim KM, Choe J, Lee C, Baik J-H, Kim YK (2017) Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex. Nat Commun 8:15730. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Petroulakis E, Wang E (2002) Nerve growth factor specifically stimulates translation of eukaryotic elongation factor 1A-1 (eEF1A-1) mRNA by recruitment to polyribosomes in PC12 cells. J Biol Chem 277:18718–18727. CrossRefGoogle Scholar
  62. 62.
    Picconi B, Piccoli G, Calabresi P (2012) Synaptic dysfunction in Parkinson’s disease. Adv Exp Med Biol 970:553–572. CrossRefGoogle Scholar
  63. 63.
    Plotegher N, Kumar D, Tessari I, Brucale M, Munari F, Tosatto L, Belluzzi E, Greggio E, Bisaglia M, Capaldi S, Aioanei D, Mammi S, Monaco HL, Samo B, Bubacco L (2014) The chaperone-like protein 14-3-3η interacts with human α-synuclein aggregation intermediates rerouting the amyloidogenic pathway and reducing α-synuclein cellular toxicity. Hum Mol Genet 23:5615–5629. CrossRefGoogle Scholar
  64. 64.
    Prots I, Veber V, Brey S, Campioni S, Buder K, Riek R, Bohm KJ, Winner B (2013) Synuclein oligomers impair neuronal microtubule-kinesin interplay. J Biol Chem 288:21742–21754. CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Ruest L-B, Marcotte R, Wang E (2002) Peptide elongation factor eEF1A-2/S1 expression in cultured differentiated myotubes and its protective effect against caspase-3-mediated apoptosis. J Biol Chem 277:5418–5425. CrossRefGoogle Scholar
  66. 66.
    Schreiner D, Savas JN, Herzog E, Brose N, de Wit J (2017) Synapse biology in the ’circuit-age’-paths toward molecular connectomics. Curr Opin Neurobiol 42:102–110. CrossRefGoogle Scholar
  67. 67.
    Scott D, Roy S (2012) α-Synuclein inhibits intersynaptic vesicle mobility and maintains recycling-pool homeostasis. J Neurosci 32:10129–10135. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Sharma K, Schmitt S, Bergner CG, Tyanova S, Kannaiyan N, Manrique-Hoyos N, Kongi K, Cantuti L, Hanisch U-K, Philips M-A, Rossner MJ, Mann M, Simons M (2015) Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci 18:1819–1831. CrossRefGoogle Scholar
  69. 69.
    Shigeoka T, Jung H, Jung J, Turner-Bridger B, Ohk J, Lin JQ, Amieux PS, Holt CE (2016) Dynamic axonal translation in developing and mature visual circuits. Cell 166:181–192. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840. CrossRefGoogle Scholar
  71. 71.
    Suzuki Y, Jin C, Iwase T, Yazawa I (2014) III Tubulin fragments inhibit—synuclein accumulation in models of multiple system atrophy. J Biol Chem 289:24374–24382. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Taylor AM, Berchtold NC, Perreau VM, Tu CH, Li Jeon N, Cotman CW (2009) Axonal mRNA in uninjured and regenerating cortical mammalian axons. J Neurosci 29:4697–4707. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580. CrossRefGoogle Scholar
  74. 74.
    Tsokas P, Grace EA, Chan P, Ma T, Sealfon SC, Iyengar R, Landau EM, Blitzer RD (2005) Local protein synthesis mediates a rapid increase in dendritic elongation factor 1A after induction of late long-term potentiation. J Neurosci 25:5833–5843. CrossRefGoogle Scholar
  75. 75.
    Vargas KJ, Makani S, Davis T, Westphal CH, Castillo PE, Chandra SS (2014) Synucleins regulate the kinetics of synaptic vesicle endocytosis. J Neurosci 34:9364–9376. CrossRefGoogle Scholar
  76. 76.
    Vizcaíno JA, Csordas A, del-Toro N, Dianes JA, Griss J, Lavidas I, Mayer G, Perez-Riverol Y, Reisinger F, Ternent T, Xu Q-W, Wang R, Hermjakob H (2016) 2016 update of the PRIDE database and its related tools. Nucleic Acids Res 44:D447–D456. CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Walker L, Stefanis L, Attems J (2019) Clinical and neuropathological differences between Parkinson’s disease, Parkinson’s disease dementia and dementia with Lewy bodies—current issues and future directions. J Neurochem. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Wang X, Huang T, Bu G, Xu H (2014) Dysregulation of protein trafficking in neurodegeneration. Mol Neurodegener 9:31CrossRefPubMedGoogle Scholar
  79. 79.
    Whittaker VP, Michaelson I, Kirkland RJA (1964) The separation of synaptic vesicles from nerve-ending particles (synaptosomes’). Biochem J 90:293PubMedPubMedCentralGoogle Scholar
  80. 80.
    Wong YC, Krainc D (2017) α-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies. Nat Med 23:1–13. CrossRefGoogle Scholar
  81. 81.
    Xu J, Wu X-S, Sheng J, Zhang Z, Yue H-Y, Sun L, Sgobio C, Lin X, Peng S, Jin Y, Gan L, Cai H, Wu L-G (2016) α-Synuclein mutation inhibits endocytosis at mammalian central nerve terminals. J Neurosci 36:4408–4414. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Yang F, Demma M, Warren V, Dharmawardhane S, Condeelis J (1990) Identification of an actin-binding protein from dictyostelium as elongation factor 1a. Nature 347:494–496. CrossRefGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Center for Neuropathology and Prion ResearchLudwig-Maximilians UniversityMunichGermany
  2. 2.German Center for Neurodegenerative Diseases (DZNE)MunichGermany
  3. 3.Université de Bordeaux, Interdisciplinary Institute for Neuroscience, UMR5297BordeauxFrance
  4. 4.CNRS, Interdisciplinary Institute for Neuroscience, UMR5297BordeauxFrance
  5. 5.Department of Biology IBiozentrum Ludwig-Maximilians UniversityMunichGermany
  6. 6.Department of Psychiatry and Psychotherapy, University HospitalLudwig-Maximilians UniversityMunichGermany
  7. 7.Plateforme Proteome, Centre Génomique Fonctionnelle de BordeauxUniversité de BordeauxBordeauxFrance
  8. 8.Munich Cluster of Systems Neurology (SyNergy)MunichGermany
  9. 9.Department Molecules-Signaling-DevelopmentMax Planck Institute of NeurobiologyMartinsriedGermany

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