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Articles

Role of the leucine-rich repeat protein kinase 2 C-terminal tail in domain cross-talk

Pallavi Kaila Sharma, Jui-Hung Weng, Jascha T. Manschwetus, Jian Wu, Wen Ma, Friedrich W. Herberg, Susan S. Taylor

Biochem J (2024) 481 (4): 313–327.

https://doi.org/10.1042/BCJ20230477

Published: 19 February 2024

... are key players in the pathogenesis of Parkinson's disease (PD). The availability of multiple structures (full-length and truncated) has opened doors to explore intra-domain cross-talk in LRRK2. A helix extending from the WD40 domain and stably docking onto the kinase domain is common in all available...

View articletitled, Role of the leucine-rich repeat protein kinase 2 C-terminal tail in domain cross-talk

Includes: Multimedia, Supplementary data

Articles

The Parkinson's disease related mutant VPS35 (D620N) amplifies the LRRK2 response to endolysosomal stress

Katy R. McCarron, Hannah Elcocks, Heather Mortiboys, Sylvie Urbé, Michael J. Clague

Biochem J (2024) 481 (4): 265–278.

https://doi.org/10.1042/BCJ20230492

Published: 15 February 2024

...Katy R. McCarron; Hannah Elcocks; Heather Mortiboys; Sylvie Urbé; Michael J. Clague The identification of multiple genes linked to Parkinson's disease (PD) invites the question as to how they may co-operate. We have generated isogenic cell lines that inducibly express either wild-type or a mutant...

View articletitled, The Parkinson's disease related mutant VPS35 (D620N) amplifies the LRRK2 response to endolysosomal stress

Includes: Supplementary data

Articles

Impact of 100 LRRK2 variants linked to Parkinson's disease on kinase activity and microtubule binding

Alexia F. Kalogeropulou, Elena Purlyte, Francesca Tonelli, Sven M. Lange, Melanie Wightman, Alan R. Prescott, Shalini Padmanabhan, Esther Sammler, Dario R. Alessi

Biochem J (2022) 479 (17): 1759–1783.

https://doi.org/10.1042/BCJ20220161

Published: 06 September 2022

...Alexia F. Kalogeropulou; Elena Purlyte; Francesca Tonelli; Sven M. Lange; Melanie Wightman; Alan R. Prescott; Shalini Padmanabhan; Esther Sammler; Dario R. Alessi Mutations enhancing the kinase activity of leucine-rich repeat kinase-2 (LRRK2) cause Parkinson's disease (PD) and therapies that reduce...

View articletitled, Impact of 100 LRRK2 variants linked to Parkinson's disease on kinase activity and microtubule binding

Includes: Supplementary data

Articles

From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease

Susanne Herbst, Patrick A. Lewis

Biochem J (2021) 478 (14): 2945–2951.

https://doi.org/10.1042/BCJ20210383

Published: 30 July 2021

...Susanne Herbst; Patrick A. Lewis Since the discovery of mutations in leucine-rich repeat kinase 2 (LRRK2) as an underlying genetic cause for the development of Parkinson's disease (PD) in 2004 (Neuron 44 , 601–607; Neuron 44 , 595–600), and subsequent efforts to develop LRRK2 kinase inhibitors...

View articletitled, From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease

Articles

Eukaryotic protein uS19: a component of the decoding site of ribosomes and a player in human diseases

Dmitri Graifer, Galina Karpova

Biochem J (2021) 478 (5): 997–1008.

https://doi.org/10.1042/BCJ20200950

Published: 04 March 2021

... with its direct involvement in the regulation of the activity of an important tumor suppressor p53 in the Mdm2/Mdmx-p53 pathway. Mutations in the RPS15 gene encoding rp uS19 are linked to diseases (Diamond Blackfan anemia, chronic lymphocytic leukemia and Parkinson's disease) caused either by defects...

View articletitled, Eukaryotic protein uS19: a component of the decoding site of ribosomes and a player in human diseases

Articles

Interaction of α-synuclein and Parkin in iron toxicity on SH-SY5Y cells: implications in the pathogenesis of Parkinson's disease

Upasana Ganguly, Anindita Banerjee, Sankha Shubhra Chakrabarti, Upinder Kaur, Oishimaya Sen, Roberto Cappai, Sasanka Chakrabarti

Biochem J (2020) 477 (6): 1109–1122.

https://doi.org/10.1042/BCJ20190676

Published: 23 March 2020

...Upasana Ganguly; Anindita Banerjee; Sankha Shubhra Chakrabarti; Upinder Kaur; Oishimaya Sen; Roberto Cappai; Sasanka Chakrabarti The toxicity of accumulated α-synuclein plays a key role in the neurodegeneration of Parkinson's disease (PD). This study has demonstrated that iron in varying...

View articletitled, Interaction of α-synuclein and Parkin in iron toxicity on SH-SY5Y cells: implications in the pathogenesis of Parkinson's disease

Includes: Supplementary data

Articles

Kinase activity of mutant LRRK2 manifests differently in hetero-dimeric vs. homo-dimeric complexes

In Collection

Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019

Emmanouela Leandrou, Eliana Markidi, Anna Memou, Katerina Melachroinou, Elisa Greggio, Hardy J. Rideout

Biochem J (2019) 476 (3): 559–579.

https://doi.org/10.1042/BCJ20180589

Published: 08 February 2019

...Emmanouela Leandrou; Eliana Markidi; Anna Memou; Katerina Melachroinou; Elisa Greggio; Hardy J. Rideout The Parkinson's disease (PD) protein leucine-rich repeat kinase 2 (LRRK2) exists as a mixture of monomeric and dimeric species, with its kinase activity highly concentrated in the dimeric...

View articletitled, Kinase activity of mutant LRRK2 manifests differently in hetero-dimeric vs. homo-dimeric complexes

Includes: Supplementary data

Articles

Validation of anti-glucocerebrosidase antibodies for western blot analysis on protein lysates of murine and human cells

Wenduo Qi, Brad A. Davidson, Matthew Nguyen, Taylor Lindstrom, Richard J. Grey, Robert Burnett, Elma Aflaki, Ellen Sidransky, Wendy Westbroek

Biochem J (2019) 476 (2): 261–274.

https://doi.org/10.1042/BCJ20180708

Published: 25 January 2019

... involved in the hydrolysis of glucosylceramide. The discovery of an association between mutations in GBA1 and the development of synucleinopathies, including Parkinson disease, has directed attention to glucocerebrosidase as a potential therapeutic target for different synucleinopathies. These findings...

View articletitled, Validation of anti-glucocerebrosidase antibodies for western blot analysis on protein lysates of murine and human cells

Articles

P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity

In Collection

Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019

Alexia F. Kalogeropulou, Jing Zhao, Marc F. Bolliger, Anna Memou, Shreya Narasimha, Tyler P. Molitor, William H. Wilson, Hardy J. Rideout, R. Jeremy Nichols

Biochem J (2018) 475 (7): 1271–1293.

https://doi.org/10.1042/BCJ20170699

Published: 09 April 2018

... to develop Parkinson's disease (PD). LRRK2 kinase activity is increased in several pathogenic mutations (N1437H, R1441C/G/H, Y1699C, G2019S), implicating hyperphosphorylation of a substrate in the pathogenesis of the disease. Identification of the downstream targets of LRRK2 is a crucial endeavor...

View articletitled, P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity

Includes: Supplementary data

Articles

Back to the future: new target-validated Rab antibodies for evaluating LRRK2 signalling in cell biology and Parkinson's disease

Patrick A. Eyers

Biochem J (2018) 475 (1): 185–189.

https://doi.org/10.1042/BCJ20170870

Published: 05 January 2018

... (LRRK2) is a Ser/Thr kinase linked to familial and sporadic cases of Parkinson's disease (PD). Recent work established that multiple Rab GTPases are physiological substrates of LRRK2, with Rab10 in particular emerging as a human substrate whose site-specific phosphorylation mirrors hyperactive LRRK2...

View articletitled, Back to the future: new target-validated Rab antibodies for evaluating LRRK2 signalling in cell biology and Parkinson's disease

Articles

Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson's disease kinase

In Collection

Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019

Pawel Lis, Sophie Burel, Martin Steger, Matthias Mann, Fiona Brown, Federico Diez, Francesca Tonelli, Janice L. Holton, Philip Winglok Ho, Shu-Leong Ho, Meng-Yun Chou, Nicole K. Polinski, Terina N. Martinez, Paul Davies, Dario R. Alessi

Biochem J (2018) 475 (1): 1–22.

https://doi.org/10.1042/BCJ20170802

Published: 02 January 2018

... kinase 2) protein kinase predispose to Parkinson's disease, suggesting that LRRK2 inhibitors might have therapeutic benefit. Recent work has revealed that LRRK2 phosphorylates a subgroup of 14 Rab proteins, including Rab10, at a specific residue located at the centre of its effector-binding switch-II...

View articletitled, Development of phospho-specific Rab protein antibodies to monitor in vivo activity of the LRRK2 Parkinson's disease kinase

Includes: Supplementary data

Articles

Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils

In Collection

Editors' pick of research highlights published in the Biochemical Journal in 2018 & 2019

Ying Fan, Andrew J.M. Howden, Adil R. Sarhan, Pawel Lis, Genta Ito, Terina N. Martinez, Kathrin Brockmann, Thomas Gasser, Dario R. Alessi, Esther M. Sammler

Biochem J (2018) 475 (1): 23–44.

https://doi.org/10.1042/BCJ20170803

Published: 02 January 2018

... access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) . biomarkers diagnostics leucine-rich repeat kinase neutrophils Parkinson's disease Rab10 PBMCs were purified from 15 ml...

View articletitled, Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils

Includes: Supplementary data

Articles

Activation mechanisms of the E3 ubiquitin ligase parkin

Nikhil Panicker, Valina L. Dawson, Ted M. Dawson

Biochem J (2017) 474 (18): 3075–3086.

https://doi.org/10.1042/BCJ20170476

Published: 31 August 2017

...Nikhil Panicker; Valina L. Dawson; Ted M. Dawson Monogenetic, familial forms of Parkinson's disease (PD) only account for 5–10% of the total number of PD cases, but analysis of the genes involved therein is invaluable to understanding PD-associated neurodegenerative signaling. One such gene, parkin...

View articletitled, Activation mechanisms of the E3 ubiquitin ligase parkin

Articles

The G2385R risk factor for Parkinson's disease enhances CHIP-dependent intracellular degradation of LRRK2

Iakov N. Rudenko, Alice Kaganovich, Rebekah G. Langston, Aleksandra Beilina, Kelechi Ndukwe, Ravindran Kumaran, Allissa A. Dillman, Ruth Chia, Mark R. Cookson

Biochem J (2017) 474 (9): 1547–1558.

https://doi.org/10.1042/BCJ20160909

Published: 24 April 2017

...Iakov N. Rudenko; Alice Kaganovich; Rebekah G. Langston; Aleksandra Beilina; Kelechi Ndukwe; Ravindran Kumaran; Allissa A. Dillman; Ruth Chia; Mark R. Cookson Autosomal dominant mutations in leucine-rich repeat kinase 2 ( LRRK2 ) are associated with Parkinson's disease (PD). Most pathogenic LRRK2...

View articletitled, The G2385R risk factor for Parkinson's disease enhances CHIP-dependent intracellular degradation of LRRK2

Includes: Supplementary data

Articles

Ubiquitin and Parkinson's disease through the looking glass of genetics

Helen Walden, Miratul M.K. Muqit

Biochem J (2017) 474 (9): 1439–1451.

https://doi.org/10.1042/BCJ20160498

Published: 13 April 2017

...Helen Walden; Miratul M.K. Muqit Biochemical alterations found in the brains of Parkinson's disease (PD) patients indicate that cellular stress is a major driver of dopaminergic neuronal loss. Oxidative stress, mitochondrial dysfunction, and ER stress lead to impairment of the homeostatic...

View articletitled, Ubiquitin and Parkinson's disease through the looking glass of genetics

Articles

Structural interface between LRRK2 and 14-3-3 protein

Loes M. Stevers, Rens M.J.M. de Vries, Richard G. Doveston, Lech-Gustav Milroy, Luc Brunsveld, Christian Ottmann

Biochem J (2017) 474 (7): 1273–1287.

https://doi.org/10.1042/BCJ20161078

Published: 23 March 2017

...Loes M. Stevers; Rens M.J.M. de Vries; Richard G. Doveston; Lech-Gustav Milroy; Luc Brunsveld; Christian Ottmann Binding of 14-3-3 proteins to leucine-rich repeat protein kinase 2 (LRRK2) is known to be impaired by many Parkinson's disease (PD)-relevant mutations. Abrogation of this interaction...

View articletitled, Structural interface between LRRK2 and 14-3-3 protein

Includes: Supplementary data

Articles

‘Up with the LRRK’: a phosphorylated Rab10 assay for evaluation of LRRK2 activity and inhibitor engagement

Patrick A. Eyers

Biochem J (2016) 473 (18): 2757–2762.

https://doi.org/10.1042/BCJ20160671C

Published: 12 September 2016

...Patrick A. Eyers Protein kinases catalyse the addition of phosphate groups to Ser/Thr and Tyr residues in cognate substrates and are mutated or hyperactive in a variety of diseases, making them important targets for rationally designed drugs. A good example is the Parkinson's disease-associated...

View articletitled, ‘Up with the LRRK’: a phosphorylated Rab10 assay for evaluation of LRRK2 activity and inhibitor engagement

Articles

Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors

Genta Ito, Kristina Katsemonova, Francesca Tonelli, Pawel Lis, Marco A.S. Baptista, Natalia Shpiro, Graham Duddy, Steve Wilson, Philip Wing-Lok Ho, Shu-Leong Ho, Alastair D. Reith, Dario R. Alessi

Biochem J (2016) 473 (17): 2671–2685.

https://doi.org/10.1042/BCJ20160557

Published: 30 August 2016

... Parkinson's disease. Recent work has revealed that LRRK2 directly phosphorylates a conserved threonine/serine residue in the effector-binding switch-II motif of a number of Rab GTPase proteins, including Rab10. Here we describe a facile and robust method to assess phosphorylation of endogenous Rab10 in mouse...

View articletitled, Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors

Includes: Supplementary data

Articles

LRRK2 and ubiquitination: implications for kinase inhibitor therapy

Heather L. Melrose

Biochem J (2015) 470 (3): e21–e24.

https://doi.org/10.1042/BJ20150785

Published: 04 September 2015

...Heather L. Melrose Pathogenic mutations and risk variants in LRRK2 (leucine-rich repeat kinase 2) represent the most common genetic cause of familial and sporadic PD (Parkinson's disease). LRRK2 protein is widely expressed throughout the brain and the periphery. Structurally, LRRK2 contains several...

View articletitled, LRRK2 and ubiquitination: implications for kinase inhibitor therapy

Articles

LRRK2 dephosphorylation increases its ubiquitination

Jing Zhao, Tyler P. Molitor, J. William Langston, R. Jeremy Nichols

Biochem J (2015) 469 (1): 107–120.

https://doi.org/10.1042/BJ20141305

Published: 19 June 2015

...Jing Zhao; Tyler P. Molitor; J. William Langston; R. Jeremy Nichols Activating mutations in the leucine rich repeat protein kinase 2 ( LRRK2 ) gene are the most common cause of inherited Parkinson's disease (PD). LRRK2 is phosphorylated on a cluster of phosphosites including Ser 910 , Ser 935 , Ser...

View articletitled, LRRK2 dephosphorylation increases its ubiquitination

Articles

DJ1 represses glycolysis and cell proliferation by transcriptionally up-regulating pink1

Raquel Requejo-Aguilar, Irene Lopez-Fabuel, Daniel Jimenez-Blasco, Emilio Fernandez, Angeles Almeida, Juan P. Bolaños

Biochem J (2015) 467 (2): 303–310.

https://doi.org/10.1042/BJ20141025

Published: 02 April 2015

... be addressed (email [email protected] ). 8 8 2014 4 2 2015 11 2 2015 11 2 2015 © The Authors Journal compilation © 2015 Biochemical Society 2015 DnaJ-1 or hsp40/hdj-1 (DJ1) is a multi-functional protein whose mutations cause autosomal recessive early-onset Parkinson's disease...

View articletitled, DJ1 represses glycolysis and cell proliferation by transcriptionally up-regulating pink1

Articles

Revisiting the Roco G-protein cycle

Susanne Terheyden, Franz Y. Ho, Bernd K. Gilsbach, Alfred Wittinghofer, Arjan Kortholt

Biochem J (2015) 465 (1): 139–147.

https://doi.org/10.1042/BJ20141095

Published: 12 December 2014

...Susanne Terheyden; Franz Y. Ho; Bernd K. Gilsbach; Alfred Wittinghofer; Arjan Kortholt Mutations in leucine-rich-repeat kinase 2 (LRRK2) are the most frequent cause of late-onset Parkinson's disease (PD). LRRK2 belongs to the Roco family of proteins which share a conserved Ras-like G-domain (Roc...

View articletitled, Revisiting the Roco G-protein cycle

Includes: Supplementary data

Articles

Switching on ubiquitylation by phosphorylating a ubiquitous activator

Gary S. Shaw

Biochem J (2014) 460 (3): e1–e3.

https://doi.org/10.1042/BJ20140459

Published: 29 May 2014

...Gary S. Shaw The dysfunction of the E3 ubiquitin ligase Parkin is a key contributor to the development of early-onset Parkinson's disease. Parkin is responsible for the labelling of outer mitochondrial membrane proteins with the small modifier protein ubiquitin in response to oxidative stress...

View articletitled, Switching on ubiquitylation by phosphorylating a ubiquitous activator

Articles

Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser 65

Agne Kazlauskaite, Chandana Kondapalli, Robert Gourlay, David G. Campbell, Maria Stella Ritorto, Kay Hofmann, Dario R. Alessi, Axel Knebel, Matthias Trost, Miratul M. K. Muqit

Biochem J (2014) 460 (1): 127–141.

https://doi.org/10.1042/BJ20140334

Published: 25 April 2014

...Agne Kazlauskaite; Chandana Kondapalli; Robert Gourlay; David G. Campbell; Maria Stella Ritorto; Kay Hofmann; Dario R. Alessi; Axel Knebel; Matthias Trost; Miratul M. K. Muqit We have previously reported that the Parkinson's disease-associated kinase PINK1 (PTEN-induced putative kinase 1...

View articletitled, Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser 65

Includes: Supplementary data

Articles

Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle

Evy Lobbestael, Jing Zhao, Iakov N. Rudenko, Aleksandra Beylina, Fangye Gao, Justin Wetter, Monique Beullens, Mathieu Bollen, Mark R. Cookson, Veerle Baekelandt, R. Jeremy Nichols, Jean-Marc Taymans

Biochem J (2013) 456 (1): 119–128.

https://doi.org/10.1042/BJ20121772

Published: 24 October 2013

... 935 , Ser 955 and Ser 973 , is important for PD (Parkinson's disease) pathogenesis as several PD-linked LRRK2 mutants are dephosphorylated at these sites. LRRK2 is also dephosphorylated in cells after pharmacological inhibition of its kinase activity, which is currently proposed as a strategy...

View articletitled, Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle

Includes: Supplementary data

Articles

Mammalian ribosomal and chaperone protein RPS3A counteracts α-synuclein aggregation and toxicity in a yeast model system

Stijn De Graeve, Sarah Marinelli, Frank Stolz, Jelle Hendrix, Jurgen Vandamme, Yves Engelborghs, Patrick Van Dijck, Johan M. Thevelein

Biochem J (2013) 455 (3): 295–306.

https://doi.org/10.1042/BJ20130417

Published: 10 October 2013

...Stijn De Graeve; Sarah Marinelli; Frank Stolz; Jelle Hendrix; Jurgen Vandamme; Yves Engelborghs; Patrick Van Dijck; Johan M. Thevelein Accumulation of aggregated forms of αSyn (α-synuclein) into Lewy bodies is a known hallmark associated with neuronal cell death in Parkinson's disease. When...

View articletitled, Mammalian ribosomal and chaperone protein RPS3A counteracts α-synuclein aggregation and toxicity in a yeast model system

Articles

Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich repeat kinase 2) monoclonal antibodies

Paul Davies, Kelly M. Hinkle, Nour N. Sukar, Bryan Sepulveda, Roxana Mesias, Geidy Serrano, Dario R. Alessi, Thomas G. Beach, Deanna L. Benson, Charles L. White, III, Rita M. Cowell, Sonal S. Das, Andrew B. West, Heather L. Melrose

Biochem J (2013) 453 (1): 101–113.

https://doi.org/10.1042/BJ20121742

Published: 13 June 2013

...) are a major cause of PD (Parkinson's disease). Several antibodies against LRRK2 have been developed, but results using these polyclonal antibodies have varied widely leading to conflicting conclusions. To address this challenge, the Michael J. Fox Foundation for Parkinson's Research generated a number...

View articletitled, Comprehensive characterization and optimization of anti-LRRK2 (leucine-rich repeat kinase 2) monoclonal antibodies

Includes: Supplementary data

Articles

Regulation of cholinergic activity by the vesicular acetylcholine transporter

Vania F. Prado, Ashbeel Roy, Benjamin Kolisnyk, Robert Gros, Marco A. M. Prado

Biochem J (2013) 450 (2): 265–274.

https://doi.org/10.1042/BJ20121662

Published: 15 February 2013

... The Authors Journal compilation © 2013 Biochemical Society 2013 Alzheimer’s disease heart failure Parkinson’s disease sepsis synaptic vesicle vascular dementia Cholinergic neurons in the CNS (central nervous system) and in the periphery secrete the neurotransmitter ACh (acetylcholine...

View articletitled, Regulation of cholinergic activity by the vesicular acetylcholine transporter

Includes: Multimedia, Supplementary data

Articles

Parkinson's disease-associated human P 5B -ATPase ATP13A2 increases spermidine uptake

Diego P. De La Hera, Gerardo R. Corradi, Hugo P. Adamo, Felicitas De Tezanos Pinto

Biochem J (2013) 450 (1): 47–53.

https://doi.org/10.1042/BJ20120739

Published: 24 January 2013

... , that belong to the P 5 -ATPase group have been identified in humans. Mutations of the human gene ATP13A2 underlie a form of PD (Parkinson's disease). Previous studies have suggested a relation between polyamines and P 5B -ATPases. We have recently shown that the cytotoxicity induced by the polyamine analogue...

View articletitled, Parkinson's disease-associated human P 5B -ATPase ATP13A2 increases spermidine uptake

Includes: Supplementary data

Articles

Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure

María Soledad Celej, Rabia Sarroukh, Erik Goormaghtigh, Gerardo D. Fidelio, Jean-Marie Ruysschaert, Vincent Raussens

Biochem J (2012) 443 (3): 719–726.

https://doi.org/10.1042/BJ20111924

Published: 16 April 2012

...María Soledad Celej; Rabia Sarroukh; Erik Goormaghtigh; Gerardo D. Fidelio; Jean-Marie Ruysschaert; Vincent Raussens Parkinson's disease is an age-related movement disorder characterized by the presence in the mid-brain of amyloid deposits of the 140-amino-acid protein AS (α-synuclein...

View articletitled, Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure

Articles

Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form

Genta Ito, Takeshi Iwatsubo

Biochem J (2012) 441 (3): 987–998.

https://doi.org/10.1042/BJ20111215

Published: 16 January 2012

...Genta Ito; Takeshi Iwatsubo Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene have been identified in PARK8, a major form of autosomal-dominantly inherited familial Parkinson's disease, although the biochemical properties of LRRK2 are not fully understood. It has been proposed that LRRK2...

View articletitled, Re-examination of the dimerization state of leucine-rich repeat kinase 2: predominance of the monomeric form

Includes: Supplementary data

Articles

Aggregation of amyloids in a cellular context: modelling and experiment

Ran Friedman

Biochem J (2011) 438 (3): 415–426.

https://doi.org/10.1042/BJ20110369

Published: 26 August 2011

... integrative biology molecular dynamics Parkinson's disease Amyloid-related diseases comprise a group of several dozen pathologies. The most common among the human amyloid-related diseases are AD (Alzheimer's disease), PD (Parkinson's disease) and T2DM (Type 2 diabetes mellitus). Other notable...

View articletitled, Aggregation of amyloids in a cellular context: modelling and experiment

Includes: Multimedia, Supplementary data

Articles

The expression of nicotinamide N -methyltransferase increases ATP synthesis and protects SH-SY5Y neuroblastoma cells against the toxicity of Complex I inhibitors

Richard B. Parsons, Shylesh Aravindan, Anusha Kadampeswaran, Emily A. Evans, Kanwaljeet K. Sandhu, Elizabeth R. Levy, Martin G. Thomas, Brian M. Austen, David B. Ramsden

Biochem J (2011) 436 (1): 145–155.

https://doi.org/10.1042/BJ20101685

Published: 27 April 2011

... expression is significantly elevated in a number of cancers, and we have previously demonstrated that NNMT expression is significantly increased in the brains of patients who have died of Parkinson's disease. To investigate the cellular effects of NNMT overexpression, we overexpressed NNMT in the SH-SY5Y...

View articletitled, The expression of nicotinamide N -methyltransferase increases ATP synthesis and protects SH-SY5Y neuroblastoma cells against the toxicity of Complex I inhibitors

Articles

14-3-3 proteins are promising LRRK2 interactors

Iakov N. Rudenko, Mark R. Cookson

Biochem J (2010) 430 (3): e5–e6.

https://doi.org/10.1042/BJ20101200

Published: 27 August 2010

...Iakov N. Rudenko; Mark R. Cookson Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common cause of familial PD (Parkinson’s disease). Mutations that cause PD are found in either the GTPase or kinase domains of LRRK2 or an intervening sequence called the COR [C-terminus of ROC (Ras...

View articletitled, 14-3-3 proteins are promising LRRK2 interactors

Articles

Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser 910 /Ser 935 , disruption of 14-3-3 binding and altered cytoplasmic localization

Nicolas Dzamko, Maria Deak, Faycal Hentati, Alastair D. Reith, Alan R. Prescott, Dario R. Alessi, R. Jeremy Nichols

Biochem J (2010) 430 (3): 405–413.

https://doi.org/10.1042/BJ20100784

Published: 27 August 2010

...Nicolas Dzamko; Maria Deak; Faycal Hentati; Alastair D. Reith; Alan R. Prescott; Dario R. Alessi; R. Jeremy Nichols LRRK2 (leucine-rich repeat protein kinase 2) is mutated in a significant number of Parkinson's disease patients. Since a common mutation that replaces Gly 2019 with a serine residue...

View articletitled, Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser 910 /Ser 935 , disruption of 14-3-3 binding and altered cytoplasmic localization

Includes: Supplementary data

Articles

14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization

R. Jeremy Nichols, Nicolas Dzamko, Nicholas A. Morrice, David G. Campbell, Maria Deak, Alban Ordureau, Thomas Macartney, Youren Tong, Jie Shen, Alan R. Prescott, Dario R. Alessi

Biochem J (2010) 430 (3): 393–404.

https://doi.org/10.1042/BJ20100483

Published: 27 August 2010

...R. Jeremy Nichols; Nicolas Dzamko; Nicholas A. Morrice; David G. Campbell; Maria Deak; Alban Ordureau; Thomas Macartney; Youren Tong; Jie Shen; Alan R. Prescott; Dario R. Alessi LRRK2 (leucine-rich repeat protein kinase 2) is mutated in a significant number of Parkinson's disease patients...

View articletitled, 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization

Includes: Supplementary data

Articles

Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease

R. Jeremy Nichols, Nicolas Dzamko, Jessica E. Hutti, Lewis C. Cantley, Maria Deak, Jennifer Moran, Paul Bamborough, Alastair D. Reith, Dario R. Alessi

Biochem J (2009) 424 (1): 47–60.

https://doi.org/10.1042/BJ20091035

Published: 23 October 2009

...R. Jeremy Nichols; Nicolas Dzamko; Jessica E. Hutti; Lewis C. Cantley; Maria Deak; Jennifer Moran; Paul Bamborough; Alastair D. Reith; Dario R. Alessi The LRRK2 (leucine-rich repeat protein kinase-2) is mutated in a significant number of Parkinson's disease patients, but little is known about its...

View articletitled, Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease

Includes: Supplementary data

Articles

New biochemical approaches towards understanding the Parkinson's disease-associated kinase, LRRK2

Geou-Yarh Liou, Kathleen A. Gallo

Biochem J (2009) 424 (1): e1–e3.

https://doi.org/10.1042/BJ20091540

Published: 23 October 2009

...Geou-Yarh Liou; Kathleen A. Gallo Some 5 years ago, it was first discovered that mutations in the gene encoding LRRK2 (leucine-rich repeat protein kinase 2) are tightly linked with a subset of familial PD (Parkinson's disease). Before this genetic association, LRRK2 had never been investigated...

View articletitled, New biochemical approaches towards understanding the Parkinson's disease-associated kinase, LRRK2

Articles

Real-time analysis of amyloid fibril formation of α-synuclein using a fibrillation-state-specific fluorescent probe of JC-1

Jung-Ho Lee, In-Hwan Lee, Young-Jun Choe, Sungsoo Kang, Hui Young Kim, Wei-Ping Gai, Ji-Sook Hahn, Seung R. Paik

Biochem J (2009) 418 (2): 311–323.

https://doi.org/10.1042/BJ20081572

Published: 11 February 2009

...Jung-Ho Lee; In-Hwan Lee; Young-Jun Choe; Sungsoo Kang; Hui Young Kim; Wei-Ping Gai; Ji-Sook Hahn; Seung R. Paik α-Synuclein is a pathological component of PD (Parkinson's disease) by participating in Lewy body formation. JC-1 (5,5′,6,6′-tetrachloro-1,1,3,3′-tetraethylbenzimidazolyl carbocyanine...

View articletitled, Real-time analysis of amyloid fibril formation of α-synuclein using a fibrillation-state-specific fluorescent probe of JC-1

Articles

Protein stability and aggregation in Parkinson's disease

Philip A. Robinson

Biochem J (2008) 413 (1): 1–13.

https://doi.org/10.1042/BJ20080295

Published: 12 June 2008

...Philip A. Robinson Parkinson's disease (PD), the second most common age-related neurodegenerative disease, results in abnormalities in motor functioning. Many fundamental questions regarding its aetiology remain unanswered. Pathologically, it is not until 70–80% of the dopaminergic neurons from...

View articletitled, Protein stability and aggregation in Parkinson's disease

Articles

Interaction with phospholipids modulates α-synuclein nitration and lipid–protein adduct formation

Andrés Trostchansky, Summer Lind, Roberto Hodara, Tomoyuki Oe, Ian A. Blair, Harry Ischiropoulos, Homero Rubbo, José M. Souza

Biochem J (2006) 393 (1): 343–349.

https://doi.org/10.1042/BJ20051277

Published: 12 December 2005

...% formic acid for ESI–MS (electrospray ionization MS) or 100 mM NH 4 HCO 3 (pH 8.5) for tryptic digestion. lipid–protein adduct neurodegenerative disorder Parkinson's disease peroxynitrite α-synuclein nitration Wild-type α-syn (α-synuclein) is a major component of Lewy bodies (LBs...

View articletitled, Interaction with phospholipids modulates α-synuclein nitration and lipid–protein adduct formation

Articles

Role of transient receptor potential canonical 6 (TRPC6) in non-transferrin-bound iron uptake in neuronal phenotype PC12 cells

James MWANJEWE, Ashok K. GROVER

Biochem J (2004) 378 (3): 975–982.

https://doi.org/10.1042/bj20031187

Published: 15 March 2004

... cells is through TRPC6, a pathway that is unique since it is receptor-stimulated. Since neuronal cells express TRPC6, this pathway may have a role in neurotoxicity. calcium channel nerve growth factor non-transferrin-bound iron Parkinson's disease PC12 cell transient receptor potential canonical...

View articletitled, Role of transient receptor potential canonical 6 (TRPC6) in non-transferrin-bound iron uptake in neuronal phenotype PC12 cells

Articles

Bicarbonate enhances alpha-synuclein oligomerization and nitration: intermediacy of carbonate radical anion and nitrogen dioxide radical

Christopher ANDREKOPOULOS, Hao ZHANG, Joy JOSEPH, Shasi KALIVENDI, B. KALYANARAMAN

Biochem J (2004) 378 (2): 435–447.

https://doi.org/10.1042/bj20031466

Published: 01 March 2004

... 2003 26 11 2003 The Biochemical Society, London ©2004 2004 Cu,Zn-superoxide dismutase (SOD1) electron spin resonance (ESR) neurodegenerative disease Parkinson's disease spin trapping α-synuclein ...

View articletitled, Bicarbonate enhances alpha-synuclein oligomerization and nitration: intermediacy of carbonate radical anion and nitrogen dioxide radical

Articles

Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines

Venugopalan D. NAIR, C. Warren OLANOW, Stuart C. SEALFON

Biochem J (2003) 373 (1): 25–32.

https://doi.org/10.1042/bj20030017

Published: 01 July 2003

...Venugopalan D. NAIR; C. Warren OLANOW; Stuart C. SEALFON Whereas dopamine agonists are known to provide symptomatic benefits for Parkinson's disease, recent clinical trials suggest that they might also be neuroprotective. Laboratory studies demonstrate that dopamine agonists can provide...

View articletitled, Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines

Articles

1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide

Shasi V. KALIVENDI, Srigiridhar KOTAMRAJU, Sonya CUNNINGHAM, Tiesong SHANG, Cecilia J. HILLARD, B. KALYANARAMAN

Biochem J (2003) 371 (1): 151–164.

https://doi.org/10.1042/bj20021525

Published: 01 April 2003

...Shasi V. KALIVENDI; Srigiridhar KOTAMRAJU; Sonya CUNNINGHAM; Tiesong SHANG; Cecilia J. HILLARD; B. KALYANARAMAN 1-Methyl-4-phenylpyridinium (MPP + ) is a neurotoxin used in cellular models of Parkinson's Disease. Although intracellular iron plays a crucial role in MPP + -induced apoptosis...

View articletitled, 1-Methyl-4-phenylpyridinium (MPP+)-induced apoptosis and mitochondrial oxidant generation: role of transferrin-receptor-dependent iron and hydrogen peroxide

Articles

Treatment of PC12 cells with nerve growth factor increases iron uptake

James MWANJEWE, Betsy King HUI, Michael D. COUGHLIN, Ashok K. GROVER

Biochem J (2001) 357 (3): 881–886.

https://doi.org/10.1042/bj3570881

Published: 25 July 2001

..., physiological saline solution; TBI, transferrin-bound iron. ascorbate dopaminergic neurons nitric oxide synthase Parkinson's disease transferrin ...

View articletitled, Treatment of PC12 cells with nerve growth factor increases iron uptake

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