Webcast - Prof Nicholas Wood - Advances in Genetic Understanding of Parkinson's Disease.

Video: Advances in Genetic Understanding of Parkinson's Disease

Webcast of the presentation entitled ‘Advances in Genetic Understanding of Parkinson's Disease’ given by Nicholas Wood (University College London, United Kingdom) presented at the Biochemical Society Hot Topic event, PINK1-Parkin Signalling in Parkinson’s Disease and Beyond, held in December 2014. More...

Pedigrees and I-FP-CIT SPECT scan images of the four families with GCH1 mutations involved in this study.

GCH1 gene and Parkinson's risk

A study published in Brain, led by researchers at UCL Institute of Neurology, has shown that genetic mutations which cause a decrease in dopamine production in the brain and lead to a form of childhood-onset Dystonia, also play a role in the development of Parkinson’s disease.

Leonard Wolfson Experimental Neurology Centre (LWENC)

The new Leonard Wolfson Experimental Neurology Centre (LWENC) has opened for clinical studies and trials


Audioslide presentation on Claudia Manzoni's paper examining how fibroblasts with LRRK2 mutations react to starvation conditions and the possible deficits that they have in autophagy.

LRRK2 and autophagy in fibroblasts

In this paper Claudia Manzoni studies how fibroblast cells from people with Parkinson’s disease caused by mutations in LRRK2 react to starvation. Although the changes are quite subtle, there are differences between the way that fibroblasts that contain mutant LRRK2 respond to being starved – suggesting that there may be changes in the way that these cells regulate a key process called autophagy (a term which comes from the greek meaning to eat yourself, and is one of the ways that cells get rid of waste and recycle proteins and organellles).

Drosophila fly model - University of Sheffield

Genetic mutations linked to Parkinson's disease

Research led by consortium researchers Dr Helene Plun-Favreau (UCL Institute of Neurology) and Dr Alex Whitworth (University of Sheffield), and collaborator Dr Heike Laman (University of Cambridge), has discovered how genetic mutations linked to Parkinson’s disease might play a key role in the death of brain cells, potentially paving the way for the development of more effective drug treatments. In the new study, published in Nature Neuroscience, the team of cross-institutional researchers showed how defects in the Parkinson’s gene Fbxo7 cause problems with mitophagy. More...

Patrick A Lewis

(Principal Investigator and Parkinson`s UK Research Fellow)

Patrick Lewis

I studied biochemistry at the University of Manchester, undertaking a year of research at the Mayo Clinic in Florida as part of this during which I investigated cellular dysfunction linked to mutations in the amyloid precursor protein and presenilin 1 associated with familial Alzheimer's disease. I then moved to the MRC Prion Unit at UCL, where I carried out graduate studies into the molecular mechanisms of scrapie gaining my PhD in 2005. From 2005 to 2007 I was visiting fellow in the Laboratory of Neurogenetics at the National Institute of Aging in Bethesda, mentored by Mark Cookson. It was here that I first started working on LRRK2, a protein which has been the object of my affections ever since. I returned to UCL in 2007 as a Brain Research Trust senior research fellow in the Department of Molecular Neuroscience and have continued my research into the basis of Parkinson's disease linked to mutations in LRRK2. I am currently a Parkinson's UK research fellow.

Laboratory webpage


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Number of items: 42.


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. 10.1016/j.chembiol.2014.05.010.

Dihanich, S; Civiero, L; Manzoni, C; Mamais, A; Bandopadhyay, R; Greggio, E; Lewis, PA; (2014) GTP binding controls complex formation by the human ROCO protein MASL1. FEBS J , 281 (1) pp. 261-274. 10.1111/febs.12593. Green open access

Mamais, A; Chia, R; Beilina, A; Hauser, DN; Hall, C; Lewis, PA; ... Bandopadhyay, R; + view all (2014) Arsenite Stress Downregulates Phosphorylation and 14-3-3 Binding of Leucine-rich Repeat Kinase 2 (LRRK2) Promoting Self-Association and Cellular Redistribution. J Biol Chem , 289 (31) pp. 21386-21400. 10.1074/jbc.M113.528463. Green open access

Tsika, E; Glauser, L; Moser, R; Fiser, A; Daniel, G; Sheerin, UM; ... Moore, DJ; + view all (2014) Parkinson's Disease-Linked Mutations in VPS35 Induce Dopaminergic Neurodegeneration. Hum Mol Genet , 23 (17) pp. 4621-4638. 10.1093/hmg/ddu178. Green open access


Burchell, VS; Nelson, DE; Sanchez-Martinez, A; Delgado-Camprubi, M; Ivatt, RM; Pogson, JH; ... Plun-Favreau, H; + view all (2013) The Parkinson's disease-linked proteins Fbxo7 and Parkin interact to mediate mitophagy. Nat Neurosci , 16 (9) 1257 - 1265. 10.1038/nn.3489.

Kara, E; Lewis, PA; Ling, H; Proukakis, C; Houlden, H; Hardy, J; (2013) α-Synuclein mutations cluster around a putative protein loop. Neurosci Lett , 546 67 - 70. 10.1016/j.neulet.2013.04.058. Green open access

Kiely, AP; Asi, YT; Kara, E; Limousin, P; Ling, H; Lewis, P; ... Holton, JL; + view all (2013) α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy? Acta Neuropathologica , 125 (5) 753 - 769. 10.1007/s00401-013-1096-7. Green open access

Mamais, A; Raja, M; Manzoni, C; Dihanich, S; Lees, A; Moore, D; ... Bandopadhyay, R; + view all (2013) Divergent α-synuclein solubility and aggregation properties in G2019S LRRK2 Parkinson's disease brains with Lewy Body pathology compared to idiopathic cases. Neurobiol Dis , 58 pp. 183-190. 10.1016/j.nbd.2013.05.017. Green open access

Manzoni, C; Lewis, PA; (2013) Dysfunction of the autophagy/lysosomal degradation pathway is a shared feature of the genetic synucleinopathies. The FASEB Journal , 27 (9) 3424 - 3429. 10.1096/fj.12-223842. Green open access

Manzoni, C; Mamais, A; Dihanich, S; Abeti, R; Soutar, MP; Plun-Favreau, H; ... Lewis, PA; + view all (2013) Inhibition of LRRK2 kinase activity stimulates macroautophagy. Biochim Biophys Acta , 1833 (12) pp. 2900-2910. 10.1016/j.bbamcr.2013.07.020. Green open access

Manzoni, C; Mamais, A; Dihanich, S; McGoldrick, P; Devine, MJ; Zerle, J; ... Lewis, PA; + view all (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. 10.1016/j.bbrc.2013.10.159.

Trabzuni, D; Ryten, M; Emmett, W; Ramasamy, A; Lackner, KJ; Zeller, T; ... Plagnol, V; + view all (2013) Fine-mapping, gene expression and splicing analysis of the disease associated LRRK2 Locus. PLOS ONE , 8 (8) , Article e70724. 10.1371/journal.pone.0070724. Green open access


Jebelli, JD; Dihanich, S; Civiero, L; Manzoni, C; Greggio, E; Lewis, PA; (2012) GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1. Sci Rep , 2 695 - ?. 10.1038/srep00695. Gold open access

Lewis, PA; (2012) Assaying the kinase activity of LRRK2 in vitro. J Vis Exp (59) 10.3791/3495. Gold open access

Lewis, PA; (2012) James Parkinson: the man behind the shaking palsy. J Parkinsons Dis , 2 (3) 181 - 187. 10.3233/JPD-2012-012108.

Lewis, PA; Alessi, DR; (2012) Deciphering the function of leucine-rich repeat kinase 2 and targeting its dysfunction in disease. Biochem Soc Trans , 40 (5) 1039 - 1041. 10.1042/BST20120178.

Lewis, PA; Cookson, MR; (2012) Gene expression in the Parkinson's disease brain. Brain Res Bull , 88 (4) 302 - 312. 10.1016/j.brainresbull.2011.11.016.

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

Patani, R; Lewis, PA; Trabzuni, D; Puddifoot, CA; Wyllie, DJ; Walker, R; ... Ryten, M; + view all (2012) Investigating the utility of human embryonic stem cell-derived neurons to model ageing and neurodegenerative disease using whole-genome gene expression and splicing analysis. J Neurochem , 122 (4) 738 - 751. 10.1111/j.1471-4159.2012.07825.x.

Wray, S; Self, M; NINDS Parkinson's Disease iPSC Consortium,; NINDS Huntington's Disease iPSC Consortium,; NINDS ALS iPSC Consortium,; Lewis, PA; ... Hardy, J; + view all (2012) Creation of an open-access, mutation-defined fibroblast resource for neurological disease research. PLOS One , 7 (8) , Article e43099. 10.1371/journal.pone.0043099. Green open access


Devine, MJ; Kaganovich, A; Ryten, M; Mamais, A; Trabzuni, D; Manzoni, C; ... Lewis, PA; + view all (2011) Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue. PLOS ONE , 6 (7) , Article e22489. 10.1371/journal.pone.0022489. Green open access

Devine, MJ; Ryten, M; Vodicka, P; Thomson, AJ; Burdon, T; Houlden, H; ... Kunath, T; + view all (2011) Parkinson's disease induced pluripotent stem cells with triplication of the alpha-synuclein locus. NAT COMMUN , 2 , Article 440. 10.1038/ncomms1453. Gold open access


Plun-Favreau, H; Lewis, PA; Hardy, J; Martins, LM; Wood, NW; (2010) Cancer and neurodegeneration: between the devil and the deep blue sea. PLoS Genetics , 6 (12) , Article e1001257. 10.1371/journal.pgen.1001257. Green open access

Wray, S; Lewis, PA; (2010) A tangled web - tau and sporadic Parkinson's disease. Front Psychiatry , 1 150 - ?. 10.3389/fpsyt.2010.00150.


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 (3) 254 - 265. 10.1016/j.gde.2009.03.008.

Lewis, PA; (2009) The function of ROCO proteins in health and disease. BIOL CELL , 101 (3) 183 - 191. 10.1042/BC20080053.

Li, YC; Dunn, L; Greggio, E; Krumm, B; Jackson, GS; Cookson, MR; ... Deng, JP; + view all (2009) The R1441C mutation alters the folding properties of the ROC domain of LRRK2. BBA-MOL BASIS DIS , 1792 (12) 1194 - 1197. 10.1016/j.bbadis.2009.09.010.


Cookson, MR; Hardy, J; Lewis, PA; (2008) Genetic Neuropathology of Parkinson's Disease. INT J CLIN EXP PATHO , 1 (3) 217 - 231. Gold open access

Deng, JP; Lewis, PA; Greggio, E; Sluch, E; Beilina, A; Cookson, MR; (2008) Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. P NATL ACAD SCI USA , 105 (5) 1499 - 1504. 10.1073/pnas.0709098105.

Devine, MJ; Lewis, PA; (2008) Emerging pathways in genetic Parkinson's disease: tangles, Lewy bodies and LRRK2. FEBS J , 275 (23) 5748 - 5757. 10.1111/j.1742-4658.2008.06707.x.

Lewis, PA; (2008) Emerging pathways in genetic Parkinson's disease. FEBS J , 275 (23) 5747 - 5747. 10.1111/j.1742-4658.2008.06706.x.


Greggio, E; Lewis, PA; van der Brug, MP; Ahmad, R; Kaganovich, A; Ding, JH; ... Cookson, MR; + view all (2007) Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1. J NEUROCHEM , 102 (1) 93 - 102. 10.1111/j.1471-4159.2007.04523.x.

Lewis, P.A.; Critchley, H.D.; Rotshtein, P.; Dolan, R.J.; (2007) Neural correlates of processing valence and arousal in affective words. Cerebral Cortex , 17 (3) pp. 742-748. 10.1093/cercor/bhk024. Green open access


Greggio, E; Jain, S; Kingsbury, A; Bandopadhyay, R; Lewis, P; Kaganovich, A; ... Cookson, MR; + view all (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. NEUROBIOL DIS , 23 (2) 329 - 341. 10.1016/j.nbd.2006.04.001.

Lewis, PA; Properzi, F; Prodromidou, K; Clarke, AR; Collinge, J; Jackson, GS; (2006) Removal of the glycosylphosphatidylinositol anchor from PrPSc by cathepsin D does not reduce prion infectivity. BIOCHEM J , 395 443 - 448. 10.1042/BJ20051677. Gold open access

Lewis, PA; Tattum, MH; Jones, S; Bhelt, D; Batchelor, M; Clarke, AR; ... Jackson, GS; + view all (2006) Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation. J GEN VIROL , 87 2443 - 2449. 10.1099/vir.0.81630-0.


Amtul, Z; Lewis, PA; Piper, S; Crook, R; Baker, M; Findlay, K; ... Golde, TE; + view all (2002) A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch. Neurobiol Dis , 9 (2) 269 - 273. 10.1006/nbdi.2001.0473.


Lewis, PA; Piper, S; Baker, M; Onstead, L; Murphy, MP; Hardy, J; ... Golde, TE; + view all (2001) Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides. Biochim Biophys Acta , 1537 (1) 58 - 62.


Houlden, H; Baker, M; McGowan, E; Lewis, P; Hutton, M; Crook, R; ... Revesz, T; + view all (2000) Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations. ANN NEUROL , 48 (5) 806 - 808.

Lewis, PA; Perez-Tur, J; Golde, TE; Hardy, J; (2000) The presenilin 1 C92S mutation increases abeta 42 production. Biochem Biophys Res Commun , 277 (1) 261 - 263. 10.1006/bbrc.2000.3646.

McLendon, C; Xin, T; Ziani-Cherif, C; Murphy, MP; Findlay, KA; Lewis, PA; ... Golde, TE; + view all (2000) Cell-free assays for gamma-secretase activity. FASEB J , 14 (15) 2383 - 2386. 10.1096/fj.00-0286fje.

Murphy, MP; Uljon, SN; Fraser, PE; Fauq, A; Lookingbill, HA; Findlay, KA; ... Golde, TE; + view all (2000) Presenilin 1 regulates pharmacologically distinct gamma -secretase activities. Implications for the role of presenilin in gamma -secretase cleavage. J Biol Chem , 275 (34) 26277 - 26284. 10.1074/jbc.M002812200. Gold open access

This list was generated on Thu Mar 26 06:18:06 2015 GMT.

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