Skip to main content
SpringerLink
Log in

LRRK2 and Autophagy

  • Chapter
  • First Online:
Leucine-Rich Repeat Kinase 2 (LRRK2)

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 14))

Abstract

Leucine-rich repeat kinase 2 (LRRK2) has been implicated in a wide range of cellular processes, including the catabolic pathways collectively described as autophagy. In this chapter, the evidence linking LRRK2 to autophagy will be examined, along with how regulation of autophagy and lysosomal pathways may provide a nexus between the physiological function of this protein and the different diseases with which it has been associated. Data from cellular and animal models for LRRK2 function and dysfunction support a role in the regulation and control of autophagic pathways in the cell, although the extant results do not provide a clear indication as to whether LRRK2 is a positive or negative regulator of these pathways, and there are conflicting data as to the impact of mutations in LRRK2 causative for Parkinson’s disease. Given that LRRK2 is a priority drug target for Parkinson’s, the evidence suggesting that knockout or inhibition of LRRK2 can result in deregulation of autophagy may have important implications and is discussed in the context of our wider understanding of LRRK2.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Yang Z, Klionsky DJ (2010) Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22(2):124–131. doi:10.1016/j.ceb.2009.11.014

    Article  CAS  PubMed  Google Scholar 

  2. Oczypok EA, Oury TD, Chu CT (2013) It’s a cell-eat-cell world: autophagy and phagocytosis. Am J Pathol 182(3):612–622. doi:10.1016/j.ajpath.2012.12.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fuchs Y, Steller H (2015) Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol 16(6):329–344. doi:10.1038/nrm3999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kaur J, Debnath J (2015) Autophagy at the crossroads of catabolism and anabolism. Nat Rev Mol Cell Biol 16(8):461–472. doi:10.1038/nrm4024

    Article  CAS  PubMed  Google Scholar 

  5. Parzych KR, Klionsky DJ (2014) An overview of autophagy: morphology, mechanism, and regulation. Antioxid Redox Signal 20(3):460–473. doi:10.1089/ars.2013.5371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Alers S, Loffler AS, Wesselborg S, Stork B (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 32(1):2–11. doi:10.1128/MCB.06159-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kang R, Zeh HJ, Lotze MT, Tang D (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18(4):571–580. doi:10.1038/cdd.2010.191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19(21):5720–5728. doi:10.1093/emboj/19.21.5720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mizushima N, Yoshimori T (2007) How to interpret LC3 immunoblotting. Autophagy 3(6):542–545

    Article  CAS  PubMed  Google Scholar 

  10. Codogno P, Mehrpour M, Proikas-Cezanne T (2012) Canonical and non-canonical autophagy: variations on a common theme of self-eating? Nat Rev Mol Cell Biol 13(1):7–12. doi:10.1038/nrm3249

    CAS  Google Scholar 

  11. Kaushik S, Cuervo AM (2012) Chaperone-mediated autophagy: a unique way to enter the lysosome world. Trends Cell Biol 22(8):407–417. doi:10.1016/j.tcb.2012.05.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Li WW, Li J, Bao JK (2012) Microautophagy: lesser-known self-eating. Cell Mol Life Sci 69(7):1125–1136. doi:10.1007/s00018-011-0865-5

    Article  CAS  PubMed  Google Scholar 

  13. Sorbara MT, Girardin SE (2015) Emerging themes in bacterial autophagy. Curr Opin Microbiol 23:163–170. doi:10.1016/j.mib.2014.11.020

    Article  CAS  PubMed  Google Scholar 

  14. Deas E, Wood NW, Plun-Favreau H (2011) Mitophagy and Parkinson’s disease: the PINK1-parkin link. Biochim Biophys Acta 1813(4):623–633. doi:10.1016/j.bbamcr.2010.08.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Manjithaya R, Nazarko TY, Farre JC, Subramani S (2010) Molecular mechanism and physiological role of pexophagy. FEBS Lett 584(7):1367–1373. doi:10.1016/j.febslet.2010.01.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wallings R, Manzoni C, Bandopadhyay R (2015) Cellular processes associated with LRRK2 function and dysfunction. FEBS J 282(15):2806–2826. doi:10.1111/febs.13305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lewis PA, Manzoni C (2012) LRRK2 and human disease: a complicated question or a question of complexes? Sci Signal 5(207):pe2. doi:10.1126/scisignal.2002680

  18. Lashuel HA, Overk CR, Oueslati A, Masliah E (2013) The many faces of alpha-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci 14(1):38–48. doi:10.1038/nrn3406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Alvarez-Erviti L, Rodriguez-Oroz MC, Cooper JM, Caballero C, Ferrer I, Obeso JA, Schapira AH (2010) Chaperone-mediated autophagy markers in Parkinson disease brains. Arch Neurol 67(12):1464–1472. doi:10.1001/archneurol.2010.198

    Article  PubMed  Google Scholar 

  20. Friedman LG, Lachenmayer ML, Wang J, He L, Poulose SM, Komatsu M, Holstein GR, Yue Z (2012) Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of alpha-synuclein and LRRK2 in the brain. J Neurosci 32(22):7585–7593. doi:10.1523/JNEUROSCI.5809-11.2012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hardy J, Lewis P, Revesz T, Lees A, Paisan-Ruiz C (2009) The genetics of Parkinson’s syndromes: a critical review. Curr Opin Genet Dev 19:254–265. doi:S0959-437X(09)00055-0 [pii]10.1016/j.gde.2009.03.008

  22. Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44(4):601–607. doi:S0896627304007202 [pii]10.1016/j.neuron.2004.11.005

  23. Wider C, Dickson DW, Wszolek ZK (2010) Leucine-rich repeat kinase 2 gene-associated disease: redefining genotype-phenotype correlation. Neurodegener Dis 7(1–3):175–179. doi:10.1159/000289232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Plowey ED, Cherra SJ, III, Liu YJ, Chu CT (2008) Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells. J Neurochem 105(3):1048–1056

    Google Scholar 

  25. Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, Wade-Martins R (2009) LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. Hum Mol Genet 18(21):4022–4034. doi:ddp346 [pii]10.1093/hmg/ddp346

  26. Gomez-Suaga P, Luzon-Toro B, Churamani D, Zhang L, Bloor-Young D, Patel S, Woodman PG, Churchill GC, Hilfiker S (2011) Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP. Hum Mol Genet 21:511–525. doi:10.1093/hmg/ddr481

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bravo-San Pedro JM, Niso-Santano M, Gomez-Sanchez R, Pizarro-Estrella E, Aiastui-Pujana A, Gorostidi A, Climent V, Lopez de Maturana R, Sanchez-Pernaute R, Lopez de Munain A, Fuentes JM, Gonzalez-Polo RA (2012) The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway. Cell Mol Life Sci 8:1537–1539. doi:10.1007/s00018-012-1061-y

    CAS  Google Scholar 

  28. Su YC, Guo X, Qi X (2015) Threonine 56 phosphorylation of Bcl-2 is required for LRRK2 G2019S-induced mitochondrial depolarization and autophagy. Biochim Biophys Acta 1852(1):12–21. doi:10.1016/j.bbadis.2014.11.009

    Article  CAS  PubMed  Google Scholar 

  29. Manzoni C, Mamais A, Dihanich S, Abeti R, Soutar MP, Plun-Favreau H, Giunti P, Tooze SA, Bandopadhyay R, Lewis PA (2013) Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim Biophys Acta 1833(12):2900–2910. doi:10.1016/j.bbamcr.2013.07.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Saez-Atienzar S, Bonet-Ponce L, Blesa JR, Romero FJ, Murphy MP, Jordan J, Galindo MF (2014) The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling. Cell Death Dis 5, e1368. doi:10.1038/cddis.2014.320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Schapansky J, Nardozzi JD, Felizia F, LaVoie MJ (2014) Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum Mol Genet 23(16):4201–4214. doi:10.1093/hmg/ddu138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Xiong Y, Coombes CE, Kilaru A, Li X, Gitler AD, Bowers WJ, Dawson VL, Dawson TM, Moore DJ (2010) GTPase activity plays a key role in the pathobiology of LRRK2. PLoS Genet 6(4), e1000902. doi:10.1371/journal.pgen.1000902

    Article  PubMed  PubMed Central  Google Scholar 

  33. Manzoni C, Mamais A, Dihanich S, McGoldrick P, Devine MJ, Zerle J, Kara E, Taanman JW, Healy DG, Marti-Masso JF, Schapira AH, Plun-Favreau H, Tooze S, Hardy J, Bandopadhyay R, Lewis PA (2013) Pathogenic Parkinson’s disease mutations across the functional domains of LRRK2 alter the autophagic/lysosomal response to starvation. Biochem Biophys Res Commun 441(4):862–866. doi:10.1016/j.bbrc.2013.10.159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Su YC, Qi X (2013) Inhibition of excessive mitochondrial fission reduced aberrant autophagy and neuronal damage caused by LRRK2 G2019S mutation. Hum Mol Genet 22(22):4545–4561. doi:10.1093/hmg/ddt301

    Article  CAS  PubMed  Google Scholar 

  35. Yakhine-Diop SM, Bravo-San Pedro JM, Gomez-Sanchez R, Pizarro-Estrella E, Rodriguez-Arribas M, Climent V, Aiastui A, Lopez de Munain A, Fuentes JM, Gonzalez-Polo RA (2014) G2019S LRRK2 mutant fibroblasts from Parkinson’s disease patients show increased sensitivity to neurotoxin 1-methyl-4-phenylpyridinium dependent of autophagy. Toxicology 324:1–9. doi:10.1016/j.tox.2014.07.001

    Article  CAS  PubMed  Google Scholar 

  36. Sanchez-Danes A, Richaud-Patin Y, Carballo-Carbajal I, Jimenez-Delgado S, Caig C, Mora S, Di Guglielmo C, Ezquerra M, Patel B, Giralt A, Canals JM, Memo M, Alberch J, Lopez-Barneo J, Vila M, Cuervo AM, Tolosa E, Consiglio A, Raya A (2012) Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol Med 4:380–395. doi:10.1002/emmm.201200215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Orenstein SJ, Kuo SH, Tasset I, Arias E, Koga H, Fernandez-Carasa I, Cortes E, Honig LS, Dauer W, Consiglio A, Raya A, Sulzer D, Cuervo AM (2013) Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16:394–406. doi:10.1038/nn.3350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Lichtenberg M, Mansilla A, Zecchini VR, Fleming A, Rubinsztein DC (2011) The Parkinson’s disease protein LRRK2 impairs proteasome substrate clearance without affecting proteasome catalytic activity. Cell Death Dis 2, e196. doi:10.1038/cddis.2011.81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Saha S, Ash PE, Gowda V, Liu L, Shirihai O, Wolozin B (2015) Mutations in LRRK2 potentiate age-related impairment of autophagic flux. Mol Neurodegener 10:26. doi:10.1186/s13024-015-0022-y

    Article  PubMed  PubMed Central  Google Scholar 

  40. Dodson MW, Leung LK, Lone M, Lizzio MA, Guo M (2014) Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo. Dis Model Mech 7(12):1351–1363. doi:10.1242/dmm.017020

    Article  PubMed  PubMed Central  Google Scholar 

  41. Marin I (2008) Ancient origin of the Parkinson disease gene LRRK2. J Mol Evol 67(1):41–50. doi:10.1007/s00239-008-9122-4

    Article  CAS  PubMed  Google Scholar 

  42. Tong Y, Yamaguchi H, Giaime E, Boyle S, Kopan R, Kelleher RJ, 3rd, Shen J (2010) Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of alpha-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A 107(21):9879–9884. doi:1004676107 [pii]10.1073/pnas.1004676107

  43. Herzig MC, Kolly C, Persohn E, Theil D, Schweizer T, Hafner T, Stemmelen C, Troxler TJ, Schmid P, Danner S, Schnell CR, Mueller M, Kinzel B, Grevot A, Bolognani F, Stirn M, Kuhn RR, Kaupmann K, van der Putten PH, Rovelli G, Shimshek DR (2011) LRRK2 protein levels are determined by kinase function and are crucial for kidney and lung homeostasis in mice. Hum Mol Genet 20(21):4209–4223. doi:10.1093/hmg/ddr348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hinkle KM, Yue M, Behrouz B, Dachsel JC, Lincoln SJ, Bowles EE, Beevers JE, Dugger B, Winner B, Prots I, Kent CB, Nishioka K, Lin WL, Dickson DW, Janus CJ, Farrer MJ, Melrose HL (2012) LRRK2 knockout mice have an intact dopaminergic system but display alterations in exploratory and motor co-ordination behaviors. Mol Neurodegener 7:25. doi:10.1186/1750-1326-7-25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Baptista MA, Dave KD, Frasier MA, Sherer TB, Greeley M, Beck MJ, Varsho JS, Parker GA, Moore C, Churchill MJ, Meshul CK, Fiske BK (2013) Loss of leucine-rich repeat kinase 2 (LRRK2) in rats leads to progressive abnormal phenotypes in peripheral organs. PLoS One 8(11), e80705. doi:10.1371/journal.pone.0080705

    Article  PubMed  PubMed Central  Google Scholar 

  46. Fuji RN, Flagella M, Baca M, Baptista MA, Brodbeck J, Chan BK, Fiske BK, Honigberg L, Jubb AM, Katavolos P, Lee DW, Lewin-Koh SC, Lin T, Liu X, Liu S, Lyssikatos JP, O’Mahony J, Reichelt M, Roose-Girma M, Sheng Z, Sherer T, Smith A, Solon M, Sweeney ZK, Tarrant J, Urkowitz A, Warming S, Yaylaoglu M, Zhang S, Zhu H, Estrada AA, Watts RJ (2015) Effect of selective LRRK2 kinase inhibition on nonhuman primate lung. Sci Transl Med 7(273):273ra215. doi:10.1126/scitranslmed.aaa3634

  47. Ramonet D, Daher JP, Lin BM, Stafa K, Kim J, Banerjee R, Westerlund M, Pletnikova O, Glauser L, Yang L, Liu Y, Swing DA, Beal MF, Troncoso JC, McCaffery JM, Jenkins NA, Copeland NG, Galter D, Thomas B, Lee MK, Dawson TM, Dawson VL, Moore DJ (2011) Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2. PLoS One 6(4), e18568. doi:10.1371/journal.pone.0018568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Tsika E, Kannan M, Foo CS, Dikeman D, Glauser L, Gellhaar S, Galter D, Knott GW, Dawson TM, Dawson VL, Moore DJ (2014) Conditional expression of Parkinson’s disease-related R1441C LRRK2 in midbrain dopaminergic neurons of mice causes nuclear abnormalities without neurodegeneration. Neurobiol Dis 71:345–358. doi:10.1016/j.nbd.2014.08.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Winslow AR, Chen CW, Corrochano S, Acevedo-Arozena A, Gordon DE, Peden AA, Lichtenberg M, Menzies FM, Ravikumar B, Imarisio S, Brown S, O’Kane CJ, Rubinsztein DC (2010) alpha-Synuclein impairs macroautophagy: implications for Parkinson’s disease. J Cell Biol 190(6):1023–1037. doi:10.1083/jcb.201003122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L (2008) Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem 283(35):23542–23556. doi:10.1074/jbc.M801992200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sidransky E, Lopez G (2012) The link between the GBA gene and parkinsonism. Lancet Neurol 11(11):986–998. doi:10.1016/S1474-4422(12)70190-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ramirez A, Heimbach A, Grundemann J, Stiller B, Hampshire D, Cid LP, Goebel I, Mubaidin AF, Wriekat AL, Roeper J, Al-Din A, Hillmer AM, Karsak M, Liss B, Woods CG, Behrens MI, Kubisch C (2006) Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 38(10):1184–1191. doi:10.1038/ng1884

    Article  CAS  PubMed  Google Scholar 

  53. Vilarino-Guell C, Wider C, Ross OA, Dachsel JC, Kachergus JM, Lincoln SJ, Soto-Ortolaza AI, Cobb SA, Wilhoite GJ, Bacon JA, Behrouz B, Melrose HL, Hentati E, Puschmann A, Evans DM, Conibear E, Wasserman WW, Aasly JO, Burkhard PR, Djaldetti R, Ghika J, Hentati F, Krygowska-Wajs A, Lynch T, Melamed E, Rajput A, Rajput AH, Solida A, Wu RM, Uitti RJ, Wszolek ZK, Vingerhoets F, Farrer MJ (2011) VPS35 mutations in Parkinson disease. Am J Hum Genet 89(1):162–167. doi:10.1016/j.ajhg.2011.06.001

    Article  PubMed  PubMed Central  Google Scholar 

  54. Hayflick SJ, Kruer MC, Gregory A, Haack TB, Kurian MA, Houlden HH, Anderson J, Boddaert N, Sanford L, Harik SI, Dandu VH, Nardocci N, Zorzi G, Dunaway T, Tarnopolsky M, Skinner S, Holden KR, Frucht S, Hanspal E, Schrander-Stumpel C, Mignot C, Heron D, Saunders DE, Kaminska M, Lin JP, Lascelles K, Cuno SM, Meyer E, Garavaglia B, Bhatia K, de Silva R, Crisp S, Lunt P, Carey M, Hardy J, Meitinger T, Prokisch H, Hogarth P (2013) beta-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation. Brain J Neurol 136(Pt 6):1708–1717. doi:10.1093/brain/awt095

  55. Manzoni C, Lewis PA (2013) Dysfunction of the autophagy/lysosomal degradation pathway is a shared feature of the genetic synucleinopathies. FASEB J 27:3424–3429. doi:10.1096/fj.12-223842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tofaris GK (2012) Lysosome-dependent pathways as a unifying theme in Parkinson’s disease. Mov Disord 27(11):1364–1369. doi:10.1002/mds.25136

    Article  CAS  PubMed  Google Scholar 

  57. Looyenga BD, Furge KA, Dykema KJ, Koeman J, Swiatek PJ, Giordano TJ, West AB, Resau JH, Teh BT, MacKeigan JP (2011) Chromosomal amplification of leucine-rich repeat kinase-2 (LRRK2) is required for oncogenic MET signaling in papillary renal and thyroid carcinomas. Proc Natl Acad Sci U S A 108(4):1439–1444. doi:10.1073/pnas.1012500108

    Article  PubMed  PubMed Central  Google Scholar 

  58. Civiero L, Dihanich S, Lewis PA, Greggio E (2014) Genetic, structural, and molecular insights into the function of ras of complex proteins domains. Chem Biol 21(7):809–818. doi:10.1016/j.chembiol.2014.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge generous funding from the Medical Research Council (grants MR/L010933/1 and MR/N026004/1), Parkinson’s UK (Fellowship F1002), the Rosetrees Trust, and the Michael J. Fox Foundation.

Conflict of Interest

The author declares no conflicts of interest.

Author information

Authors and Affiliations

  1. School of Pharmacy, University of Reading, Whiteknights, Reading, UK

    Claudia Manzoni & Patrick A. Lewis

  2. Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK

    Claudia Manzoni & Patrick A. Lewis

Authors
  1. Claudia Manzoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick A. Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick A. Lewis .

Editor information

Editors and Affiliations

  1. Biomedical Research Foundation of the Academy of Athens (BRFAA), Athens, Greece

    Hardy J. Rideout

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Manzoni, C., Lewis, P.A. (2017). LRRK2 and Autophagy. In: Rideout, H. (eds) Leucine-Rich Repeat Kinase 2 (LRRK2). Advances in Neurobiology, vol 14. Springer, Cham. https://doi.org/10.1007/978-3-319-49969-7_5

Download citation

Publish with us

Policies and ethics

Search

Navigation