CoChat
Sign Up
Cited by 32

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

Inhibition of LRRK2 kinase activity promotes anterograde axonal transport and presynaptic targeting of α-synuclein

Brzozowski, Charlotte F., Hijaz, Baraa A., Singh, Vijay, Gcwensa, Nolwazi Z., Kelly, Kaela, Boyden, Edward S., West, Andrew B., Sarkar, Deblina, Volpicelli-Daley, Laura A.·2021·Acta Neuropathologica Communications
DOI 10.1186/s40478-021-01283-7PMC PMC8576889

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Pathologic inclusions composed of α-synuclein called Lewy pathology are hallmarks of Parkinson’s Disease (PD). Dominant inherited mutations in leucine rich repeat kinase 2 (LRRK2) are the most common genetic cause of PD. Lewy pathology is found in the majority of individuals with LRRK2-PD, particularly those with the G2019S-LRRK2 mutation. Lewy pathology in LRRK2-PD associates with increased non-motor symptoms such as cognitive deficits, anxiety, and orthostatic hypotension. Thus, understanding the relationship between LRRK2 and α-synuclein could be important for determining the mechanisms of non-motor symptoms. In PD models, expression of mutant LRRK2 reduces membrane localization of α-synuclein, and enhances formation of pathologic α-synuclein, particularly when synaptic activity is increased. α-Synuclein and LRRK2 both localize to the presynaptic terminal. LRRK2 plays a role in membrane traffic, including axonal transport, and therefore may influence α-synuclein synaptic localization. This study shows that LRRK2 kinase activity influences α-synuclein targeting to the presynaptic terminal. We used the selective LRRK2 kinase inhibitors, MLi-2 and PF-06685360 (PF-360) to determine the impact of reduced LRRK2 kinase activity on presynaptic localization of α-synuclein. Expansion microscopy (ExM) in primary hippocampal cultures and the mouse striatum, in vivo, was used to more precisely resolve the presynaptic localization of α-synuclein. Live imaging of axonal transport of α-synuclein-GFP was used to investigate the impact of LRRK2 kinase inhibition on α-synuclein axonal transport towards the presynaptic terminal. Reduced LRRK2 kinase activity increases α-synuclein overlap with presynaptic markers in primary neurons, and increases anterograde axonal transport of α-synuclein-GFP. In vivo, LRRK2 inhibition increases α-synuclein overlap with glutamatergic, cortico-striatal terminals, and dopaminergic nigral-striatal presynaptic terminals. The findings suggest that LRRK2 kinase activity plays a role in axonal transport, and presynaptic targeting of α-synuclein. These data provide potential mechanisms by which LRRK2-mediated perturbations of α-synuclein localization could cause pathology in both LRRK2-PD, and idiopathic PD.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/s40478-021-01283-7

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

1 retracted

Flagged first, then by citations

Show all 3 references

Research works printed but not linked: 92

  1. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839–840 · DOI · Paper page
  2. Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, de Lopez MA, Aparicio S, Gil AM, Khan N et al (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron 44(4):595–600 · DOI
  3. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44(4):601–607 · DOI
  4. Di Maio R, Hoffman EK, Rocha EM, Keeney MT, Sanders LH, De Miranda BR, Zharikov A, Van Laar A, Stepan AF, Lanz TA et al (2018) LRRK2 activation in idiopathic Parkinson’s disease. Science translational medicine 10(451):67 · DOI
  5. Kalia LV, Lang AE, Hazrati LN, Fujioka S, Wszolek ZK, Dickson DW, Ross OA, Van Deerlin VM, Trojanowski JQ, Hurtig HI et al (2015) Clinical correlations with Lewy body pathology in LRRK2-related Parkinson disease. JAMA Neurol 72(1):100–105 · DOI
  6. Bieri G, Brahic M, Bousset L, Couthouis J, Kramer NJ, Ma R, Nakayama L, Monbureau M, Defensor E, Schule B et al (2019) LRRK2 modifies alpha-syn pathology and spread in mouse models and human neurons. Acta Neuropathol 137(6):961–980 · DOI
  7. Lin X, Parisiadou L, Gu XL, Wang L, Shim H, Sun L, Xie C, Long CX, Yang WJ, Ding J et al (2009) Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson’s-disease-related mutant alpha-synuclein. Neuron 64(6):807–827 · DOI
  8. Schapansky J, Khasnavis S, DeAndrade MP, Nardozzi JD, Falkson SR, Boyd JD, Sanderson JB, Bartels T, Melrose HL, LaVoie MJ (2018) Familial knockin mutation of LRRK2 causes lysosomal dysfunction and accumulation of endogenous insoluble alpha-synuclein in neurons. Neurobiol Dis 111:26–35 · DOI
  9. Volpicelli-Daley LA, Abdelmotilib H, Liu Z, Stoyka L, Daher JP, Milnerwood AJ, Unni VK, Hirst WD, Yue Z, Zhao HT et al (2016) G2019S-LRRK2 expression augments alpha-synuclein sequestration into inclusions in neurons. J Neurosci Offic J Soc Neurosci 36(28):7415–7427 · DOI
  10. Zhao HT, John N, Delic V, Ikeda-Lee K, Kim A, Weihofen A, Swayze EE, Kordasiewicz HB, West AB, Volpicelli-Daley LA (2017) LRRK2 antisense oligonucleotides ameliorate alpha-synuclein inclusion formation in a parkinson’s disease mouse model. Mol Ther Nucleic Acids 8:508–519 · DOI
  11. Atias M, Tevet Y, Sun J, Stavsky A, Tal S, Kahn J, Roy S, Gitler D (2019) Synapsins regulate alpha-synuclein functions. Proc Natl Acad Sci USA 116(23):11116–11118 · DOI
  12. Burre J, Sharma M, Tsetsenis T, Buchman V, Etherton MR, Sudhof TC (2010) Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science (New York, NY) 329(5999):1663–1667 · DOI
  13. Sun J, Wang L, Bao H, Premi S, Das U, Chapman ER, Roy S (2019) Functional cooperation of alpha-synuclein and VAMP2 in synaptic vesicle recycling. Proc Natl Acad Sci USA 116(23):11113–11115 · DOI
  14. Taguchi K, Watanabe Y, Tsujimura A, Tanaka M (2016) Brain region-dependent differential expression of alpha-synuclein. J Comp Neurol 524(6):1236–1258 · DOI
  15. Vargas KJ, Schrod N, Davis T, Fernandez-Busnadiego R, Taguchi YV, Laugks U, Lucic V, Chandra SS (2017) Synucleins have multiple effects on presynaptic architecture. Cell Rep 18(1):161–173 · DOI
  16. Ysselstein D, Joshi M, Mishra V, Griggs AM, Asiago JM, McCabe GP, Stanciu LA, Post CB, Rochet JC (2015) Effects of impaired membrane interactions on α-synuclein aggregation and neurotoxicity. Neurobiol Dis 79:150–163 · DOI
  17. Arranz AM, Delbroek L, Van Kolen K, Guimarães MR, Mandemakers W, Daneels G, Matta S, Calafate S, Shaban H, Baatsen P et al (2015) LRRK2 functions in synaptic vesicle endocytosis through a kinase-dependent mechanism. J Cell Sci 128(3):541–552
  18. Cirnaru MD, Marte A, Belluzzi E, Russo I, Gabrielli M, Longo F, Arcuri L, Murru L, Bubacco L, Matteoli M et al (2014) LRRK2 kinase activity regulates synaptic vesicle trafficking and neurotransmitter release through modulation of LRRK2 macro-molecular complex. Front Mol Neurosci 7:49 · DOI · Paper page
  19. Matikainen-Ankney BA, Kezunovic N, Menard C, Flanigan ME, Zhong Y, Russo SJ, Benson DL, Huntley GW (2018) Parkinson’s disease-linked LRRK2-G2019S mutation alters synaptic plasticity and promotes resilience to chronic social stress in young adulthood. J Neurosci Off J Soc Neurosci 38(45):9700–9711 · DOI · Paper page
  20. Pan PY, Zhu Y, Shen Y, Yue Z (2019) Crosstalk between presynaptic trafficking and autophagy in Parkinson’s disease. Neurobiol Dis 122:64–71 · DOI
  21. Hu D, Niu JY, Xiong J, Nie SK, Zeng F, Zhang ZH (2018) LRRK2 G2019S mutation inhibits degradation of alpha-synuclein in an in vitro model of Parkinson’s disease. Curr Med Sci 38(6):1012–1017 · DOI
  22. Pischedda F, Piccoli G (2021) LRRK2 at the pre-synaptic site: a 16-years perspective. J Neurochem 157(2):297–311 · DOI
  23. Matta S, Van Kolen K, da Cunha R, van den Bogaart G, Mandemakers W, Miskiewicz K, De Bock PJ, Morais VA, Vilain S, Haddad D et al (2012) LRRK2 controls an EndoA phosphorylation cycle in synaptic endocytosis. Neuron 75(6):1008–1021 · DOI · Paper page
  24. Cookson MR (2016) Cellular functions of LRRK2 implicate vesicular trafficking pathways in Parkinson’s disease. Biochem Soc Trans 44(6):1603–1610 · DOI
  25. Boecker CA, Holzbaur ELF (2021) Hyperactive LRRK2 kinase impairs the trafficking of axonal autophagosomes. Autophagy 2:1–3
  26. Boecker CA, Goldsmith J, Dou D, Cajka GG, Holzbaur ELF (2021) Increased LRRK2 kinase activity alters neuronal autophagy by disrupting the axonal transport of autophagosomes. Current biology : CB 31(10):2140-2154.e2146 · DOI
  27. Godena VK, Brookes-Hocking N, Moller A, Shaw G, Oswald M, Sancho RM, Miller CC, Whitworth AJ, De Vos KJ (2014) Increasing microtubule acetylation rescues axonal transport and locomotor deficits caused by LRRK2 Roc-COR domain mutations. Nat Commun 5:5245 · DOI
  28. Burre J, Sharma M, Sudhof TC (2015) Definition of a molecular pathway mediating alpha-synuclein neurotoxicity. J Neurosci Off J Soc Neurosci 35(13):5221–5232 · DOI
  29. Burre J, Sharma M, Sudhof TC (2014) alpha-Synuclein assembles into higher-order multimers upon membrane binding to promote SNARE complex formation. Proc Natl Acad Sci USA 111(40):E4274-4283 · DOI
  30. Dettmer U, Newman AJ, von Saucken VE, Bartels T, Selkoe D (2015) KTKEGV repeat motifs are key mediators of normal alpha-synuclein tetramerization: their mutation causes excess monomers and neurotoxicity. Proc Natl Acad Sci USA 112(31):9596–9601 · DOI
  31. Fusco G, De Simone A, Arosio P, Vendruscolo M, Veglia G, Dobson CM (2016) Structural ensembles of membrane-bound α-Synuclein reveal the molecular determinants of synaptic vesicle affinity. Sci Rep 6:27125 · DOI
  32. Fusco G, De Simone A, Gopinath T, Vostrikov V, Vendruscolo M, Dobson CM, Veglia G (2014) Direct observation of the three regions in alpha-synuclein that determine its membrane-bound behaviour. Nat Commun 5:3827 · DOI
  33. Fonseca-Ornelas L, Eisbach SE, Paulat M, Giller K, Fernandez CO, Outeiro TF, Becker S, Zweckstetter M (2014) Small molecule-mediated stabilization of vesicle-associated helical alpha-synuclein inhibits pathogenic misfolding and aggregation. Nat Commun 5:5857 · DOI
  34. Burre J, Sharma M, Sudhof TC (2012) Systematic mutagenesis of alpha-synuclein reveals distinct sequence requirements for physiological and pathological activities. J Neurosci Off J Soc Neurosci 32(43):15227–15242 · DOI
  35. Dettmer U, Newman AJ, von Saucken VE, Bartels T, Selkoe D (2015) KTKEGV repeat motifs are key mediators of normal α-synuclein tetramerization: their mutation causes excess monomers and neurotoxicity. Proc Natl Acad Sci USA 112(31):9596–9601 · DOI
  36. Dettmer U, Newman AJ, Soldner F, Luth ES, Kim NC, von Saucken VE, Sanderson JB, Jaenisch R, Bartels T, Selkoe D (2015) Parkinson-causing α-synuclein missense mutations shift native tetramers to monomers as a mechanism for disease initiation. Nat Commun 6:7314 · DOI · Paper page
  37. Volpicelli-Daley LA, Gamble KL, Schultheiss CE, Riddle DM, West AB, Lee VM (2014) Formation of alpha-synuclein Lewy neurite-like aggregates in axons impedes the transport of distinct endosomes. Mol Biol Cell 25(25):4010–4023 · DOI
  38. Wu Q, Shaikh MA, Meymand ES, Zhang B, Luk KC, Trojanowski JQ, Lee VM (2020) Neuronal activity modulates alpha-synuclein aggregation and spreading in organotypic brain slice cultures and in vivo. Acta Neuropathol 140(6):831–849 · DOI
  39. Fortin DL, Nemani VM, Voglmaier SM, Anthony MD, Ryan TA, Edwards RH (2005) Neural activity controls the synaptic accumulation of alpha-synuclein. J Neurosci Off J Soc Neurosci 25(47):10913–10921 · DOI
  40. Diao J, Burre J, Vivona S, Cipriano DJ, Sharma M, Kyoung M, Sudhof TC, Brunger AT (2013) Native alpha-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2. eLife 2:e00592 · DOI
  41. Gao R, Asano SM, Upadhyayula S, Pisarev I, Milkie DE, Liu TL, Singh V, Graves A, Huynh GH, Zhao Y et al (2019) Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution. Science (New York, NY) 363(6424):15900 · DOI
  42. Karagiannis ED, Boyden ES (2018) Expansion microscopy: development and neuroscience applications. Curr Opin Neurobiol 50:56–63 · DOI
  43. Kelly K, Wang S, Boddu R, Liu Z, Moukha-Chafiq O, Augelli-Szafran C, West AB (2018) The G2019S mutation in LRRK2 imparts resiliency to kinase inhibition. Exp Neurol 309:1–13 · DOI
  44. Volpicelli-Daley LA, Luk KC, Lee VM (2014) Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy neurite-like aggregates. Nat Protoc 9(9):2135–2146 · DOI · Paper page
  45. Roy S, Winton MJ, Black MM, Trojanowski JQ, Lee VM (2008) Cytoskeletal requirements in axonal transport of slow component-b. J Neurosci Off J Soc Neurosci 28(20):5248–5256 · DOI
  46. Roy S, Winton MJ, Black MM, Trojanowski JQ, Lee VM (2007) Rapid and intermittent cotransport of slow component-b proteins. J Neurosci Off J Soc Neurosci 27(12):3131–3138 · DOI
  47. Volpicelli-Daley LA (2017) Effects of α-synuclein on axonal transport. Neurobiol Dis 105:321–327 · DOI
  48. Chen F, Tillberg PW, Boyden ES (2015) Optical imaging. Expansion microscopy. Science (New York, NY) 347(6221):543–548 · DOI
  49. Sarkar D, Kang J, Wassie AT, Schroeder ME, Peng Z, Tarr TB, Tang A-H, Niederst E, Young JZ, Tsai L-H et al (2020) Expansion revealing: decrowding proteins to unmask invisible brain nanostructures. bioRxiv 20:12696
  50. Stoyka LE, Mahoney CL, Thrasher DR, Russell DL, Cook AK, Harris AT, Narayanan A, Janado TP, Standaert DG, Roberson ED et al (2021) Templated α-synuclein inclusion formation is independent of endogenous Tau. eNeuro 8(3):1205 · DOI
  51. Lee SH, Valtschanoff JG, Kharazia VN, Weinberg R, Sheng M (2001) Biochemical and morphological characterization of an intracellular membrane compartment containing AMPA receptors. Neuropharmacology 41(6):680–692 · DOI
  52. Taguchi K, Watanabe Y, Tsujimura A, Tanaka M (2019) Expression of alpha-synuclein is regulated in a neuronal cell type-dependent manner. Anat Sci Int 94(1):11–22 · DOI
  53. West AB, Cowell RM, Daher JP, Moehle MS, Hinkle KM, Melrose HL, Standaert DG, Volpicelli-Daley LA (2014) Differential LRRK2 expression in the cortex, striatum, and substantia nigra in transgenic and nontransgenic rodents. J Comp Neurol 522(11):2465–2480 · DOI · Paper page
  54. Matikainen-Ankney BA, Kezunovic N, Mesias RE, Tian Y, Williams FM, Huntley GW, Benson DL (2016) Altered development of synapse structure and function in striatum caused by Parkinson’s disease-linked LRRK2-G2019S mutation. J Neurosci Off J Soc Neurosci 36(27):7128–7141 · DOI · Paper page
  55. Chen C, Soto G, Dumrongprechachan V, Bannon N, Kang S, Kozorovitskiy Y, Parisiadou L (2020) Pathway-specific dysregulation of striatal excitatory synapses by LRRK2 mutations. eLife 9:102056 · DOI · Paper page
  56. Volta M, Beccano-Kelly DA, Paschall SA, Cataldi S, MacIsaac SE, Kuhlmann N, Kadgien CA, Tatarnikov I, Fox J, Khinda J et al (2017) Initial elevations in glutamate and dopamine neurotransmission decline with age, as does exploratory behavior, in LRRK2 G2019S knock-in mice. eLife 6:1059 · DOI · Paper page
  57. Fell MJ, Mirescu C, Basu K, Cheewatrakoolpong B, DeMong DE, Ellis JM, Hyde LA, Lin Y, Markgraf CG, Mei H et al (2015) MLi-2, a potent, selective, and centrally active compound for exploring the therapeutic potential and safety of LRRK2 kinase inhibition. J Pharmacol Exp Ther 355(3):397–409 · DOI
  58. Sheng Z, Zhang S, Bustos D, Kleinheinz T, Le Pichon CE, Dominguez SL, Solanoy HO, Drummond J, Zhang X, Ding X et al (2012) Ser1292 autophosphorylation is an indicator of LRRK2 kinase activity and contributes to the cellular effects of PD mutations. Sci Transl Med 4(164):164ra161 · DOI
  59. Chang JB, Chen F, Yoon YG, Jung EE, Babcock H, Kang JS, Asano S, Suk HJ, Pak N, Tillberg PW et al (2017) Iterative expansion microscopy. Nat Methods 14(6):593–599 · DOI
  60. Dzamko N, Deak M, Hentati F, Reith AD, Prescott AR, Alessi DR, Nichols RJ (2010) Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization. Biochem J 430(3):405–413 · DOI
  61. Zhao Y, Dzamko N (2019) Recent developments in LRRK2-targeted therapy for Parkinson’s disease. Drugs 79(10):1037–1051 · DOI
  62. Benson DL, Matikainen-Ankney BA, Hussein A, Huntley GW (2018) Functional and behavioral consequences of Parkinson’s disease-associated LRRK2-G2019S mutation. Biochem Soc Trans 46(6):1697–1705 · DOI
  63. Ysselstein D, Nguyen M, Young TJ, Severino A, Schwake M, Merchant K, Krainc D (2019) LRRK2 kinase activity regulates lysosomal glucocerebrosidase in neurons derived from Parkinson’s disease patients. Nat Commun 10(1):5570 · DOI
  64. Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M et al (2014) Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson’s disease. Cell 157(2):472–485 · DOI · Paper page
  65. Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I, Cortes E, Honig LS, Dauer W, Consiglio A et al (2013) Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16(4):394–406 · DOI · Paper page
  66. Hur EM, Jang EH, Jeong GR, Lee BD (2019) LRRK2 and membrane trafficking: nexus of Parkinson’s disease. BMB Rep 52(9):533–539 · DOI
  67. Gcwensa NZ, Russell DL, Cowell RM, Volpicelli-Daley LA (2021) Molecular mechanisms underlying synaptic and axon degeneration in Parkinson’s disease. Front Cell Neurosci 15:626128 · DOI · Paper page
  68. Boassa D, Berlanga ML, Yang MA, Terada M, Hu J, Bushong EA, Hwang M, Masliah E, George JM, Ellisman MH (2013) Mapping the subcellular distribution of alpha-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: implications for Parkinson’s disease pathogenesis. J Neurosci Off J Soc Neurosci 33(6):2605–2615 · DOI
  69. Clayton DF, George JM (1999) Synucleins in synaptic plasticity and neurodegenerative disorders. J Neurosci Res 58(1):120–129 · DOI
  70. Maroteaux L, Campanelli JT, Scheller RH (1988) Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. J Neurosci Off J Soc Neurosci 8(8):2804–2815 · DOI
  71. Vargas KJ, Makani S, Davis T, Westphal CH, Castillo PE, Chandra SS (2014) Synucleins regulate the kinetics of synaptic vesicle endocytosis. J Neurosci Off J Soc Neurosci 34(28):9364–9376 · DOI
  72. Kuhlmann N, Milnerwood AJ (2020) A critical LRRK at the synapse? The neurobiological function and pathophysiological dysfunction of LRRK2. Front Mol Neurosci 13(153):1609
  73. Beccano-Kelly DA, Kuhlmann N, Tatarnikov I, Volta M, Munsie LN, Chou P, Cao L-P, Han H, Tapia L, Farrer MJ et al (2014) Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice. Front Cell Neurosci 8(301):1023
  74. Gureviciene I, Gurevicius K, Tanila H (2007) Role of alpha-synuclein in synaptic glutamate release. Neurobiol Dis 28(1):83–89 · DOI
  75. Lee SK, Sillitoe RV, Silva C, Martina M, Sekerkova G (2015) alpha-Synuclein expression in the mouse cerebellum is restricted to VGluT1 excitatory terminals and is enriched in unipolar brush cells. Cerebellum (London, England) 14(5):516–527 · DOI
  76. Wang L, Das U, Scott DA, Tang Y, McLean PJ, Roy S (2014) alpha-synuclein multimers cluster synaptic vesicles and attenuate recycling. Current Biol 24(19):2319–2326 · DOI
  77. Cheng F, Vivacqua G, Yu S (2011) The role of alpha-synuclein in neurotransmission and synaptic plasticity. J Chem Neuroanat 42(4):242–248 · DOI
  78. Scott D, Roy S (2012) alpha-Synuclein inhibits intersynaptic vesicle mobility and maintains recycling-pool homeostasis. J Neurosci Off J Soc Neurosci 32(30):10129–10135 · DOI
  79. Foffani G, Obeso JA (2018) A cortical pathogenic theory of Parkinson’s disease. Neuron 99(6):1116–1128 · DOI
  80. Marte A, Russo I, Rebosio C, Valente P, Belluzzi E, Pischedda F, Montani C, Lavarello C, Petretto A, Fedele E et al (2019) Leucine-rich repeat kinase 2 phosphorylation on synapsin I regulates glutamate release at pre-synaptic sites. J Neurochem 150(3):264–281 · DOI
  81. Piccoli G, Condliffe SB, Bauer M, Giesert F, Boldt K, De Astis S, Meixner A, Sarioglu H, Vogt-Weisenhorn DM, Wurst W et al (2011) LRRK2 controls synaptic vesicle storage and mobilization within the recycling pool. J Neurosci Off J Soc Neurosci 31(6):2225–2237 · DOI
  82. Butler B, Saha K, Rana T, Becker JP, Sambo D, Davari P, Goodwin JS, Khoshbouei H (2015) Dopamine transporter activity is modulated by alpha-synuclein. J Biol Chem 290(49):29542–29554 · DOI
  83. Artzi M, Even-Sapir E, Lerman SH, Thaler A, Urterger AO, Bressman S, Marder K, Hendler T, Giladi N, Ben BD et al (2017) DaT-SPECT assessment depicts dopamine depletion among asymptomatic G2019S LRRK2 mutation carriers. PloS one 12(4):e0175424 · DOI
  84. Longhena F, Faustini G, Missale C, Pizzi M, Bellucci A (2018) Dopamine transporter/α-synuclein complexes are altered in the post mortem caudate putamen of Parkinson’s disease: an in situ proximity ligation assay study. Int J Mol Sci 19(6):10296 · DOI
  85. Tang Y, Das U, Scott DA, Roy S (2012) The slow axonal transport of alpha-synuclein–mechanistic commonalities amongst diverse cytosolic cargoes. Cytoskeleton (Hoboken, NJ) 69(7):506–513 · DOI
  86. Chevalier-Larsen E, Holzbaur EL (2006) Axonal transport and neurodegenerative disease. Biochem Biophys Acta 1762(11–12):1094–1108
  87. Deniston CK, Salogiannis J, Mathea S, Snead DM, Lahiri I, Matyszewski M, Donosa O, Watanabe R, Böhning J, Shiau AK et al (2020) Structure of LRRK2 in Parkinson’s disease and model for microtubule interaction. Nature 588(7837):344–349 · DOI
  88. Maday S, Twelvetrees AE, Moughamian AJ, Holzbaur EL (2014) Axonal transport: cargo-specific mechanisms of motility and regulation. Neuron 84(2):292–309 · DOI · Paper page
  89. Lis P, Burel S, Steger M, Mann M, Brown F, Diez F, Tonelli F, Holton JL, Ho PW, Ho SL et al (2018) Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson’s disease kinase. Biochem J 475(1):1–22 · DOI · Paper page
  90. Seol W, Nam D, Son I (2019) Rab GTPases as physiological substrates of LRRK2 kinase. Exp Neurobiol 28(2):134–145 · DOI
  91. Steger M, Diez F, Dhekne HS, Lis P, Nirujogi RS, Karayel O, Tonelli F, Martinez TN, Lorentzen E, Pfeffer SR et al (2017) Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis. eLife 6:8742 · DOI · Paper page
  92. Steger M, Tonelli F, Ito G, Davies P, Trost M, Vetter M, Wachter S, Lorentzen E, Duddy G, Wilson S et al (2016) Phosphoproteomics reveals that Parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5:120369 · DOI · Paper page

Cited by

Sorted by citations

See all 32

Metadata

Authors
Brzozowski, C. F., Hijaz, B. A., Singh, V., Gcwensa, N. Z., Kelly, K., Boyden, E. S., West, A. B., Sarkar, D., & Volpicelli-Daley, L. A.
Venue
Acta Neuropathologica Communications
Publisher
Springer Science and Business Media LLC
Published
2021-11-08
Volume
9
Issue
1
ISSN
2051-5960
DOI
10.1186/s40478-021-01283-7
PMC
PMC8576889
Cited by
32
References
3
Language
en
Licence
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS102257, R56NS117465)
  • Michael J. Fox Foundation for Parkinson's Research (MJFF-004413)
  • National Institute of Health (1R01EB024261)
  • Howard Hughes Medical Institute

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review