LRRK2

LRRK2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2ZEJ, 3D6T
Identifikatori
Aliasi	LRRK2
Vanjski ID-jevi	OMIM: 609007 MGI: 1913975 HomoloGene: 18982 GeneCards: LRRK2
EC broj	2.7.11.1
Lokacija gena (čovjek)
Hrom.	Hromosom 12 (čovjek)
Kraj	40,369,285 bp
Lokacija gena (miš)
Hrom.	Hromosom 15 (miš)
Kraj	91,700,323 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein homodimerization activity; • signaling receptor complex adaptor activity; • clathrin binding; • co-receptor binding; • transferase activity; • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity; • protein kinase activity; • protein kinase A binding; • peroxidase inhibitor activity; • SNARE binding; • nucleotide binding; • vezivanje identičnih proteina; • GO:0006184 GTPase activity; • syntaxin-1 binding; • protein serine/threonine kinase activity; • vezivanje tubulina; • transmembrane transporter binding; • microtubule binding; • MAP kinase kinase activity; • GTP binding; • ATP binding; • GTP-dependent protein kinase activity; • beta-catenin destruction complex binding; • GO:0001948, GO:0016582 vezivanje za proteine; • kinase activity; • actin binding; • magnesium ion binding;
Ćelijska komponenta	• GO:0016023 citoplazmatska vezikula; • endozom; • Egzosom; • Wnt signalosome; • neuronal cell body; • trans-Golđijeva mreža; • mitochondrial membranes; • sinapsa; • citoplazma; • mitochondrial outer membrane; • synaptic vesicle membrane; • perikaryon; • Endoplazmatski retikulum; • ćelijska membrana; • microvillus; • mitochondrial matrix; • dendrite cytoplasm; • growth cone; • projekcija ćelije; • dendrit; • Lizozom; • neuron projection; • Golgi-associated vesicle; • mitohondrija; • mitochondrial inner membrane; • autolysosome; • terminal bouton; • intracellular anatomical structure; • membrana; • Lipidni splav; • Akson; • amphisome; • multivesicular body, internal vesicle; • Sinapsna vezikula; • inclusion body; • međućelijske veze; • cytoplasmic side of mitochondrial outer membrane; • citosol; • Golđijev aparat; • postsynapse; • Vanćelijsko; • jedro; • intracellular membrane-bounded organelle; • caveola neck; • endoplasmic reticulum exit site; • glutamatergic synapse; • presynaptic cytosol; • ribonukleoprotein;
Biološki proces	• lysosome organization; • GO:0001306 response to oxidative stress; • cellular response to dopamine; • regulation of autophagy; • positive regulation of autophagy; • positive regulation of dopamine receptor signaling pathway; • regulation of neuroblast proliferation; • intracellular distribution of mitochondria; • negative regulation of protein processing; • negative regulation of protein processing involved in protein targeting to mitochondrion; • protein localization to mitochondrion; • positive regulation of canonical Wnt signaling pathway; • Autofagija; • neuromuscular junction development; • Fosforilacija; • positive regulation of protein binding; • regulation of branching morphogenesis of a nerve; • mitochondrion localization; • positive regulation of protein autoubiquitination; • regulation of synaptic vesicle transport; • positive regulation of protein phosphorylation; • regulation of kidney size; • regulation of synaptic vesicle exocytosis; • positive regulation of MAP kinase activity; • peptidyl-threonine phosphorylation; • MAPK cascade; • Wnt signalosome assembly; • protein phosphorylation; • regulation of synaptic transmission, glutamatergic; • excitatory postsynaptic potential; • negative regulation of hydrogen peroxide-induced cell death; • regulation of dopamine receptor signaling pathway; • regulation of membrane potential; • protein autophosphorylation; • regulation of mitochondrial fission; • regulation of neuron maturation; • reactive oxygen species metabolic process; • positive regulation of programmed cell death; • regulation of neuron death; • regulation of mitochondrial depolarization; • cellular response to oxidative stress; • negative regulation of late endosome to lysosome transport; • GO:0007243 intracellular signal transduction; • regulation of lysosomal lumen pH; • GO:0034259 negative regulation of GTPase activity; • locomotory exploration behavior; • Golgi organization; • canonical Wnt signaling pathway; • neuron projection morphogenesis; • positive regulation of protein ubiquitination; • regulation of canonical Wnt signaling pathway; • exploration behavior; • GO:1904579 cellular response to organic cyclic compound; • tangential migration from the subventricular zone to the olfactory bulb; • regulation of protein kinase A signaling; • calcium-mediated signaling; • negative regulation of thioredoxin peroxidase activity by peptidyl-threonine phosphorylation; • negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; • positive regulation of proteasomal ubiquitin-dependent protein catabolic process; • negative regulation of neuron death; • negative regulation of protein targeting to mitochondrion; • GO:0035404 peptidyl-serine phosphorylation; • determination of adult lifespan; • negative regulation of excitatory postsynaptic potential; • GO:0033128 negative regulation of protein phosphorylation; • neuron death; • GTP metabolic process; • negative regulation of autophagosome assembly; • olfactory bulb development; • cellular response to starvation; • regulation of dendritic spine morphogenesis; • Ćelijska diferencijacija; • Endocitoza; • negative regulation of protein binding; • mitochondrion organization; • cellular response to manganese ion; • negative regulation of macroautophagy; • regulation of locomotion; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • regulation of retrograde transport, endosome to Golgi; • regulation of CAMKK-AMPK signaling cascade; • positive regulation of histone deacetylase activity; • endoplasmic reticulum organization; • Spermatogeneza; • Regulacija ekspresije gena; • negative regulation of neuron projection development; • striatum development; • regulation of protein stability; • positive regulation of nitric-oxide synthase biosynthetic process; • regulation of ER to Golgi vesicle-mediated transport; • protein localization to endoplasmic reticulum exit site; • neuron projection arborization; • regulation of synaptic vesicle endocytosis; • positive regulation of synaptic vesicle endocytosis; • positive regulation of microglial cell activation; • protein import into nucleus;
	Izvori:Amigo / QuickGO
Ortolozi
	120892
	66725
	ENSG00000188906
	ENSMUSG00000036273
	Q5S007
	Q5S006
	NM_198578
	NM_025730
	NP_940980
	NP_080006
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Leucinom bogata ponavljajuća kinaza 2 (LRRK2), znano i kao dardarin (od baskijske riječi dardara što znači drhtanje) i PARK8 (od ranije identificirane povezanosti s Parkinsonovom bolešću), je kinazni enzim koji je kod ljudi kodiran genom LRRK2.^[5] LRRK2 je član kinazne porodice leucinski bogatih enzima. Varijante ovog grna povezuju se sa Parkinsonovo i Crohnovom bolešču.^[5]^[6]

Aminokiselinska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 2.527 aminokiselina, a molekulska težina 286.103 Da.^[7]

10	20	30	40	50
MASGSCQGCE	EDEETLKKLI	VRLNNVQEGK	QIETLVQILE	DLLVFTYSER
ASKLFQGKNI	HVPLLIVLDS	YMRVASVQQV	GWSLLCKLIE	VCPGTMQSLM
GPQDVGNDWE	VLGVHQLILK	MLTVHNASVN	LSVIGLKTLD	LLLTSGKITL
LILDEESDIF	MLIFDAMHSF	PANDEVQKLG	CKALHVLFER	VSEEQLTEFV
ENKDYMILLS	ALTNFKDEEE	IVLHVLHCLH	SLAIPCNNVE	VLMSGNVRCY
NIVVEAMKAF	PMSERIQEVS	CCLLHRLTLG	NFFNILVLNE	VHEFVVKAVQ
QYPENAALQI	SALSCLALLT	ETIFLNQDLE	EKNENQENDD	EGEEDKLFWL
EACYKALTWH	RKNKHVQEAA	CWALNNLLMY	QNSLHEKIGD	EDGHFPAHRE
VMLSMLMHSS	SKEVFQASAN	ALSTLLEQNV	NFRKILLSKG	IHLNVLELMQ
KHIHSPEVAE	SGCKMLNHLF	EGSNTSLDIM	AAVVPKILTV	MKRHETSLPV
QLEALRAILH	FIVPGMPEES	REDTEFHHKL	NMVKKQCFKN	DIHKLVLAAL
NRFIGNPGIQ	KCGLKVISSI	VHFPDALEML	SLEGAMDSVL	HTLQMYPDDQ
EIQCLGLSLI	GYLITKKNVF	IGTGHLLAKI	LVSSLYRFKD	VAEIQTKGFQ
TILAILKLSA	SFSKLLVHHS	FDLVIFHQMS	SNIMEQKDQQ	FLNLCCKCFA
KVAMDDYLKN	VMLERACDQN	NSIMVECLLL	LGADANQAKE	GSSLICQVCE
KESSPKLVEL	LLNSGSREQD	VRKALTISIG	KGDSQIISLL	LRRLALDVAN
NSICLGGFCI	GKVEPSWLGP	LFPDKTSNLR	KQTNIASTLA	RMVIRYQMKS
AVEEGTASGS	DGNFSEDVLS	KFDEWTFIPD	SSMDSVFAQS	DDLDSEGSEG
SFLVKKKSNS	ISVGEFYRDA	VLQRCSPNLQ	RHSNSLGPIF	DHEDLLKRKR
KILSSDDSLR	SSKLQSHMRH	SDSISSLASE	REYITSLDLS	ANELRDIDAL
SQKCCISVHL	EHLEKLELHQ	NALTSFPQQL	CETLKSLTHL	DLHSNKFTSF
PSYLLKMSCI	ANLDVSRNDI	GPSVVLDPTV	KCPTLKQFNL	SYNQLSFVPE
NLTDVVEKLE	QLILEGNKIS	GICSPLRLKE	LKILNLSKNH	ISSLSENFLE
ACPKVESFSA	RMNFLAAMPF	LPPSMTILKL	SQNKFSCIPE	AILNLPHLRS
LDMSSNDIQY	LPGPAHWKSL	NLRELLFSHN	QISILDLSEK	AYLWSRVEKL
HLSHNKLKEI	PPEIGCLENL	TSLDVSYNLE	LRSFPNEMGK	LSKIWDLPLD
ELHLNFDFKH	IGCKAKDIIR	FLQQRLKKAV	PYNRMKLMIV	GNTGSGKTTL
LQQLMKTKKS	DLGMQSATVG	IDVKDWPIQI	RDKRKRDLVL	NVWDFAGREE
FYSTHPHFMT	QRALYLAVYD	LSKGQAEVDA	MKPWLFNIKA	RASSSPVILV
GTHLDVSDEK	QRKACMSKIT	KELLNKRGFP	AIRDYHFVNA	TEESDALAKL
RKTIINESLN	FKIRDQLVVG	QLIPDCYVEL	EKIILSERKN	VPIEFPVIDR
KRLLQLVREN	QLQLDENELP	HAVHFLNESG	VLLHFQDPAL	QLSDLYFVEP
KWLCKIMAQI	LTVKVEGCPK	HPKGIISRRD	VEKFLSKKRK	FPKNYMSQYF
KLLEKFQIAL	PIGEEYLLVP	SSLSDHRPVI	ELPHCENSEI	IIRLYEMPYF
PMGFWSRLIN	RLLEISPYML	SGRERALRPN	RMYWRQGIYL	NWSPEAYCLV
GSEVLDNHPE	SFLKITVPSC	RKGCILLGQV	VDHIDSLMEE	WFPGLLEIDI
CGEGETLLKK	WALYSFNDGE	EHQKILLDDL	MKKAEEGDLL	VNPDQPRLTI
PISQIAPDLI	LADLPRNIML	NNDELEFEQA	PEFLLGDGSF	GSVYRAAYEG
EEVAVKIFNK	HTSLRLLRQE	LVVLCHLHHP	SLISLLAAGI	RPRMLVMELA
SKGSLDRLLQ	QDKASLTRTL	QHRIALHVAD	GLRYLHSAMI	IYRDLKPHNV
LLFTLYPNAA	IIAKIADYGI	AQYCCRMGIK	TSEGTPGFRA	PEVARGNVIY
NQQADVYSFG	LLLYDILTTG	GRIVEGLKFP	NEFDELEIQG	KLPDPVKEYG
CAPWPMVEKL	IKQCLKENPQ	ERPTSAQVFD	ILNSAELVCL	TRRILLPKNV
IVECMVATHH	NSRNASIWLG	CGHTDRGQLS	FLDLNTEGYT	SEEVADSRIL
CLALVHLPVE	KESWIVSGTQ	SGTLLVINTE	DGKKRHTLEK	MTDSVTCLYC
NSFSKQSKQK	NFLLVGTADG	KLAIFEDKTV	KLKGAAPLKI	LNIGNVSTPL
MCLSESTNST	ERNVMWGGCG	TKIFSFSNDF	TIQKLIETRT	SQLFSYAAFS
DSNIITVVVD	TALYIAKQNS	PVVEVWDKKT	EKLCGLIDCV	HFLREVMVKE
NKESKHKMSY	SGRVKTLCLQ	KNTALWIGTG	GGHILLLDLS	TRRLIRVIYN
FCNSVRVMMT	AQLGSLKNVM	LVLGYNRKNT	EGTQKQKEIQ	SCLTVWDINL
PHEVQNLEKH	IEVRKELAEK	MRRTSVE

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Funkcija[uredi | uredi izvor]

Gen LRRK2 kodira protein sa ponavljajućom armadilo (ARM) regijom, pnavljajućom ankirinskom (ANK) regijom, domenima leucinski bogatog ponavljanja (LRR), kinaze, RAS, GTPaza i WD40. Protein je prisutan uglavnom u citoplazmi, ali se povezuje i sa vanjskom mitohondrijskom membranom.

LRRK2 stupa u interakciju sa C-terminalnim R2 domenom RING prsta parkin, a parkin u interakciju sa COR domenom LRRK2. Ekspresija se javlja u mutantima apoptotske ćelijske smrti, izazvane mutacijom LRRK2 u ćelijama neuroblastoma i u mišjim korteksnim neuronima.^[8]

Ekspresija mutanata LRRK2 upletena u autosomno dominantnu Parkinsonovu bolest uzrokuje skraćivanje i pojednostavljivanje dendritskog stabla in vivo i u kultiviranim neuronima (in vitro).^[9] Posredovano je djelimično i izmjenama u makroautofagiji,^[10]^[11]^[12]^[13]^[14] i može se prevenirati protein-kinazom A, putem regulacije autopfagijskog proteina LC3.^[15] Mutacije G2019S i R1441C izazivaju postsinapsnu neravnotežu kalcija, što mitofagijom dovodi do viška mitohondrijskog klirensa dendrita.^[16] LRRK2 je također supstrat za šaperonski posredovanu autofagiju.^[17]

Klinički značaj[uredi | uredi izvor]

Mutacije u ovom genu su povezane sa Parkinsonovom bolešćutype 8.^[18]

Mutacija Gly2019Ser rezultira povećanom aktivnošću kinaze i relativno je čest uzrok porodične Parkinsonove bolesti kod kavkazoida.^[19] Može uzrokovati i sporadičnu Parkinsonovu bolest. Mutirana Gly aminokiselina konzervirana je u svim kinaznim domenima svih vrsta.

Mutacija Gly2019Ser jedna je od malog broja mutacija LRRK2 za koje je dokazano da uzrokuju Parkinsonovu bolest. Od njih, Gly2019Ser je najčešći u zapadnom svijetu i čini ~2% svih slučajeva Parkinsonove bolesti u sjevernoameričkih kavkazoida. Ova mutacija je učestalija je u određenim populacijama, a nalazi se u približno 20% svih pacijenata s Aškenazi jevrejskom Parkinsonovom bolešću i u približno 40% svih pacijenata s Parkinsonovom bolešću sjevernoafričkog berberskog porijekla.^[20]^[21]

Neočekivano, studije pridruživanja širom genoma otkrile su povezanost između LRRK2 i Crohnove bolesti, kao i s Parkinsonovom bolešću, što ukazuje na to da dvije bolesti imaju zajedničke puteve.^[22]^[23]

Napravljeni su pokušaji uzgoja kristala LRRK2 na brodu Međunarodne svemirske stanica, jer okruženje niske gravitacije čini protein manje osjetljivim na sedimentaciju i konvekciju, pa se stoga može kristalizirati.^[24]

Mutacije u genu LRRK2 glavni su faktor koji doprinosi genetičkoj osnovi i razvoju Parkinsonove bolesti (PD), a pokazalo se da preko 100 mutacija u ovom genu povećava šanse za razvoj PD. Ove mutacije najčešće su u sjevernoafričkim arapskim berberskim, kineskim i japanskim populacijama.^[25]

Reference[uredi | uredi izvor]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000188906 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000036273 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Paisán-Ruíz C, Jain S, Evans EW, Gilks WP, Simón J, van der Brug M, López de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Martí-Massó JF, Pérez-Tur J, Wood NW, Singleton AB (novembar 2004). "Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease". Neuron. 44 (4): 595–600. doi:10.1016/j.neuron.2004.10.023. PMID 15541308. S2CID 16688488.
^ 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, Müller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T (novembar 2004). "Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology". Neuron. 44 (4): 601–7. doi:10.1016/j.neuron.2004.11.005. PMID 15541309. S2CID 8642468.
^ "UniProt, Q5S007". Pristupljeno 11. 8. 2021.
^ Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, Dawson VL, Dawson TM, Ross CA (decembar 2005). "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration". Proceedings of the National Academy of Sciences of the United States of America. 102 (51): 18676–81. Bibcode:2005PNAS..10218676S. doi:10.1073/pnas.0508052102. PMC 1317945. PMID 16352719.
^ MacLeod D, Dowman J, Hammond R, Leete T, Inoue K, Abeliovich A (novembar 2006). "The familial Parkinsonism gene LRRK2 regulates neurite process morphology". Neuron. 52 (4): 587–93. doi:10.1016/j.neuron.2006.10.008. PMID 17114044. S2CID 16966163.
^ Plowey ED, Cherra SJ, Liu YJ, Chu CT (maj 2008). "Role of autophagy in G2019S-LRRK2-associated neurite shortening in differentiated SH-SY5Y cells". Journal of Neurochemistry. 105 (3): 1048–56. doi:10.1111/j.1471-4159.2008.05217.x. PMC 2361385. PMID 18182054.
^ Friedman LG, Lachenmayer ML, Wang J, He L, Poulose SM, Komatsu M, Holstein GR, Yue Z (maj 2012). "Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain". The Journal of Neuroscience. 32 (22): 7585–93. doi:10.1523/JNEUROSCI.5809-11.2012. PMC 3382107. PMID 22649237.
^ Gómez-Suaga P, Luzón-Toro B, Churamani D, Zhang L, Bloor-Young D, Patel S, Woodman PG, Churchill GC, Hilfiker S (februar 2012). "Leucine-rich repeat kinase 2 regulates autophagy through a calcium-dependent pathway involving NAADP". Human Molecular Genetics. 21 (3): 511–25. doi:10.1093/hmg/ddr481. PMC 3259011. PMID 22012985.
^ 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 (april 2011). Cai H (ured.). "Dopaminergic neuronal loss, reduced neurite complexity and autophagic abnormalities in transgenic mice expressing G2019S mutant LRRK2". PLOS ONE. 6 (4): e18568. Bibcode:2011PLoSO...618568R. doi:10.1371/journal.pone.0018568. PMC 3071839. PMID 21494637.
^ Alegre-Abarrategui J, Christian H, Lufino MM, Mutihac R, Venda LL, Ansorge O, Wade-Martins R (novembar 2009). "LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model". Human Molecular Genetics. 18 (21): 4022–34. doi:10.1093/hmg/ddp346. PMC 2758136. PMID 19640926.
^ Cherra SJ, Kulich SM, Uechi G, Balasubramani M, Mountzouris J, Day BW, Chu CT (august 2010). "Regulation of the autophagy protein LC3 by phosphorylation". The Journal of Cell Biology. 190 (4): 533–9. doi:10.1083/jcb.201002108. PMC 2928022. PMID 20713600.
^ Cherra SJ, Steer E, Gusdon AM, Kiselyov K, Chu CT (februar 2013). "Mutant LRRK2 elicits calcium imbalance and depletion of dendritic mitochondria in neurons". The American Journal of Pathology. 182 (2): 474–84. doi:10.1016/j.ajpath.2012.10.027. PMC 3562730. PMID 23231918.
^ 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 (april 2013). "Interplay of LRRK2 with chaperone-mediated autophagy". Nature Neuroscience. 16 (4): 394–406. doi:10.1038/nn.3350. PMC 3609872. PMID 23455607.
^ "Entrez Gene: LRRK2 leucine-rich repeat kinase 2".
^ Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW (februar 2005). "A common LRRK2 mutation in idiopathic Parkinson's disease". Lancet. 365 (9457): 415–6. doi:10.1016/S0140-6736(05)17830-1. PMID 15680457. S2CID 36186136.
^ Healy DG, Falchi M, O'Sullivan SS, Bonifati V, Durr A, Bressman S, et al. (juli 2008). "Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study". The Lancet. Neurology. 7 (7): 583–90. doi:10.1016/S1474-4422(08)70117-0. PMC 2832754. PMID 18539534.
^ Lesage S, Dürr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, et al. (januar 2006). "LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs". The New England Journal of Medicine. 354 (4): 422–3. doi:10.1056/NEJMc055540. PMID 16436781.
^ Manolio TA (juli 2010). "Genomewide association studies and assessment of the risk of disease". The New England Journal of Medicine. 363 (2): 166–76. doi:10.1056/NEJMra0905980. PMID 20647212.
^ Nalls MA, Plagnol V, Hernandez DG, Sharma M, Sheerin UM, Saad M, Simón-Sánchez J, Schulte C, Lesage S, Sveinbjörnsdóttir S, Stefánsson K, Martinez M, Hardy J, Heutink P, Brice A, Gasser T, Singleton AB, Wood NW (februar 2011). "Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies". Lancet. 377 (9766): 641–9. doi:10.1016/S0140-6736(10)62345-8. PMC 3696507. PMID 21292315.
^ Carreau, Mark (14. 11. 2018). "ISS Cargo Missions To Test Soyuz, Deliver New Science". Aviation Week. A collaboration between the Michael J. Fox Foundation, of New York City, and Merck Research Laboratories, of Kenilworth, New Jersey, will seek to grow crystals of a key gene protein, Leucine-Rich Repeat Kinase 2 (LRRK2), in an effort to advance the search for a cure for Parkinson’s disease. Crystals cultured in the absence of gravity are less susceptible to sedimentation and convection, rendering them larger and easier to map than those grown in labs on Earth in order to design medicines.
^ “Young-Onset Parkinson's.” Parkinson's Foundation, 2 Oct. 2018, www.parkinson.org/Understanding-Parkinsons/What-is-Parkinsons/Young-Onset-Parkinsons.

Dopunska literatura[uredi | uredi izvor]

Singleton AB (august 2005). "Altered alpha-synuclein homeostasis causing Parkinson's disease: the potential roles of dardarin". Trends in Neurosciences. 28 (8): 416–21. doi:10.1016/j.tins.2005.05.009. PMID 15955578. S2CID 53204736.
Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA (maj 2006). "LRRK2 in Parkinson's disease: protein domains and functional insights". Trends in Neurosciences. 29 (5): 286–93. doi:10.1016/j.tins.2006.03.006. PMID 16616379. S2CID 11458231.
Haugarvoll K, Wszolek ZK (juli 2006). "PARK8 LRRK2 parkinsonism". Current Neurology and Neuroscience Reports. 6 (4): 287–94. doi:10.1007/s11910-006-0020-0. PMID 16822348. S2CID 25252449.
Bonifati V (septembar 2006). "The pleomorphic pathology of inherited Parkinson's disease: lessons from LRRK2". Current Neurology and Neuroscience Reports. 6 (5): 355–7. doi:10.1007/s11910-996-0013-z. PMID 16928343. S2CID 41352829.
Schapira AH (septembar 2006). "The importance of LRRK2 mutations in Parkinson disease". Archives of Neurology. 63 (9): 1225–8. doi:10.1001/archneur.63.9.1225. PMID 16966498.
Whaley NR, Uitti RJ, Dickson DW, Farrer MJ, Wszolek ZK (2006). "Clinical and pathologic features of families with LRRK2-associated Parkinson's disease". Parkinson's Disease and Related Disorders. Journal of Neural Transmission. Supplementum. str. 221–229. doi:10.1007/978-3-211-45295-0_34. ISBN 978-3-211-28927-3. PMID 17017533.
Gasser, T. (2006). "Molecular genetic findings in LRRK2 American, Canadian and German families". Parkinson's Disease and Related Disorders. Journal of Neural Transmission. Supplementum. str. 231–234. doi:10.1007/978-3-211-45295-0_35. ISBN 978-3-211-28927-3. PMID 17017534.
Tan EK (novembar 2006). "Identification of a common genetic risk variant (LRRK2 Gly2385Arg) in Parkinson's disease". Annals of the Academy of Medicine, Singapore. 35 (11): 840–2. PMID 17160203.

Vanjski linkovi[uredi | uredi izvor]

GeneReviews/NCBI/NIH/UW entry on LRRK2-Related Parkinson Disease
LRRK2 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000188906 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000036273 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

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[UniProt-7] "UniProt, Q5S007". Pristupljeno 11. 8. 2021.

[pmid16352719-8] Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, Dawson VL, Dawson TM, Ross CA (decembar 2005). "Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration". Proceedings of the National Academy of Sciences of the United States of America. 102 (51): 18676–81. Bibcode:2005PNAS..10218676S. doi:10.1073/pnas.0508052102. PMC 1317945. PMID 16352719.

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[21] Lesage S, Dürr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, et al. (januar 2006). "LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs". The New England Journal of Medicine. 354 (4): 422–3. doi:10.1056/NEJMc055540. PMID 16436781.

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[24] Carreau, Mark (14. 11. 2018). "ISS Cargo Missions To Test Soyuz, Deliver New Science". Aviation Week. A collaboration between the Michael J. Fox Foundation, of New York City, and Merck Research Laboratories, of Kenilworth, New Jersey, will seek to grow crystals of a key gene protein, Leucine-Rich Repeat Kinase 2 (LRRK2), in an effort to advance the search for a cure for Parkinson’s disease. Crystals cultured in the absence of gravity are less susceptible to sedimentation and convection, rendering them larger and easier to map than those grown in labs on Earth in order to design medicines.

[25] “Young-Onset Parkinson's.” Parkinson's Foundation, 2 Oct. 2018, www.parkinson.org/Understanding-Parkinsons/What-is-Parkinsons/Young-Onset-Parkinsons.

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