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Keywords: Parkinson’s disease
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Articles
Biochem Soc Trans (2023) 51 (2): 797–809.
Published: 06 April 2023
...Mario K. Shammas; Tzu-Hsiang Huang; Derek P. Narendra In the last decade, dominant mutations in the mitochondrial protein CHCHD10 (p.R15L and p.S59L) and its paralog CHCHD2 (p.T61I) were shown to cause familial amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), respectively...
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Biochem Soc Trans (2023) 51 (2): 587–595.
Published: 17 March 2023
...Rachel Fasiczka; Yahaira Naaldijk; Besma Brahmia; Sabine Hilfiker Point mutations in leucine-rich repeat kinase 2 (LRRK2) which cause Parkinson's disease increase its kinase activity, and a subset of Rab GTPases have been identified as endogenous LRRK2 kinase substrates. Their phosphorylation...
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Biochem Soc Trans (2021) 49 (3): 1375–1384.
Published: 07 May 2021
...Alice Filippini; Massimo Gennarelli; Isabella Russo Missense mutations in the leucine-rich repeat kinase-2 ( LRRK2 ) gene represent the most common cause of autosomal dominant Parkinson's disease (PD). In the years LRRK2 has been associated with several organelles and related pathways in cell...
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Biochem Soc Trans (2020) 48 (5): 2185–2194.
Published: 20 October 2020
...Ahmed Soliman; Fatma Nihan Cankara; Arjan Kortholt Parkinson's disease (PD) is the second most common neurodegenerative disease. In recent years, it has been shown that leucine-rich repeat kinase 2 (LRRK2) has a crucial function in both familial and sporadic forms of PD. LRRK2 pathogenic mutations...
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Biochem Soc Trans (2020) 48 (4): 1795–1806.
Published: 14 August 2020
...). Evidence of immature, wild-type SOD1 misfolding has also been observed in sporadic ALS, non-SOD1 familial ALS and Parkinson's disease. The copper chaperone for SOD1 (hCCS) is a dedicated and specific chaperone that assists SOD1 folding and maturation to produce the active enzyme. Misfolded or misfolding...
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Biochem Soc Trans (2019) 47 (6): 1581–1595.
Published: 26 November 2019
...Rebecca L. Wallings; Malú G. Tansey Mutations in the leucine-rich-repeat kinase 2 ( LRRK2 ) gene are associated with familial and sporadic cases of Parkinson's disease but are also found in immune-related disorders such as inflammatory bowel disease, tuberculosis and leprosy. LRRK2 is highly...
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Biochem Soc Trans (2019) 47 (3): 827–838.
Published: 13 May 2019
...Tiago Fleming Outeiro; Kirsten Harvey; Antonio Dominguez-Meijide; Ellen Gerhardt The identification of genetic forms of Parkinson's disease (PD) has tremendously expanded our understanding of the players and mechanisms involved. Mutations in the genes encoding for alpha-synuclein (aSyn), LRRK2...
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Biochem Soc Trans (2019) 47 (2): 651–661.
Published: 05 March 2019
...Jillian H. Kluss; Adamantios Mamais; Mark R. Cookson The past two decades in research has revealed the importance of leucine-rich repeat kinase 2 (LRRK2) in both monogenic and sporadic forms of Parkinson's disease (PD). In families, mutations in LRRK2 can cause PD with age-dependent but variable...
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Biochem Soc Trans (2018) 46 (6): 1653–1663.
Published: 22 November 2018
...Laura Civiero; Susanna Cogo; Alice Biosa; Elisa Greggio Leucine-rich repeat kinase 2 (LRRK2), a complex kinase/GTPase mutated in Parkinson's disease, has been shown to physically and functionally interact with cytoskeletal-related components in different brain cells. Neurons greatly rely...
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Biochem Soc Trans (2018) 46 (6): 1707–1712.
Published: 22 November 2018
...Suzanne R. Pfeffer Leucine-rich repeat kinase 2 (LRRK2) is mutated in familial Parkinson's disease, and pathogenic mutations activate the kinase activity. A tour de force screen by Mann and Alessi and co-workers identified a subset of Rab GTPases as bona fide LRRK2 substrates. Rab GTPases...
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Biochem Soc Trans (2017) 45 (1): 113–122.
Published: 15 February 2017
...Mattia Volta; Heather Melrose Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of familial Parkinson's disease (PD), resembling the sporadic disorder. Intensive effort has been directed toward LRRK2 mouse modeling and investigation, aimed at reproducing the human...
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Biochem Soc Trans (2017) 45 (1): 163–172.
Published: 15 February 2017
...Md. Shariful Islam; Darren J. Moore Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are the most common cause of familial Parkinson's disease (PD) with autosomal dominant inheritance. Accordingly, LRRK2 has emerged as a promising therapeutic target for disease modification in PD. Since...
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Biochem Soc Trans (2017) 45 (1): 155–162.
Published: 15 February 2017
..., therefore, controlling a plethora of diverse functions based on the different complexes formed. Among these, I will then focus on macroautophagy in the general context of the endolysosomal system. First, the relevance of autophagy in Parkinson's disease will be evaluated giving a brief overview of all...
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Biochem Soc Trans (2017) 45 (1): 141–146.
Published: 15 February 2017
...Marian Blanca Ramírez; Antonio Jesús Lara Ordóñez; Elena Fdez; Sabine Hilfiker Mutations in the Leucine-Rich Repeat Kinase 2 ( LRRK2 ) gene are intimately linked to both familial and sporadic Parkinson's disease. LRRK2 is a large protein kinase able to bind and hydrolyse GTP. A wealth of in vitro...
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Biochem Soc Trans (2017) 45 (1): 261–267.
Published: 15 February 2017
...Elisa Greggio; Luigi Bubacco; Isabella Russo Evidence indicates that leucine-rich repeat kinase 2 (LRRK2) controls multiple processes in neurons and glia cells. Deregulated LRRK2 activity due to gene mutation represents the most common cause of autosomal dominant Parkinson's disease (PD). Protein...
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Biochem Soc Trans (2016) 44 (6): 1611–1616.
Published: 02 December 2016
...Susanne Terheyden; Laura M. Nederveen-Schippers; Arjan Kortholt Mutations in the human leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of hereditary Parkinson's disease (PD). LRRK2 belongs to the Roco family of proteins, which are characterized by the presence of a Ras of complex...
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Biochem Soc Trans (2016) 44 (6): 1625–1634.
Published: 02 December 2016
...Jonathon Nixon-Abell; Daniel C. Berwick; Kirsten Harvey Leucine-rich repeat kinase 2 (LRRK2) is a central protein in the pathogenesis of Parkinson's disease (PD), yet its normal function has proved stubbornly hard to elucidate. Even though it remains unclear how pathogenic mutations affect LRRK2...
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Biochem Soc Trans (2015) 43 (2): 292–296.
Published: 07 April 2015
... of neuronal polarity, axonal transport and synaptic plasticity. The concept that MT dysfunction can participate in, and perhaps lead to, Parkinson's disease (PD) progression has been suggested by studies using toxin-based and genetic experimental models of the disease. Here, we first learn lessons from MPTP...
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Biochem Soc Trans (2015) 43 (2): 280–286.
Published: 07 April 2015
...Liesbeth Aerts; Bart De Strooper; Vanessa A. Morais PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] is a serine/threonine kinase targeted to mitochondria and implicated in early-onset recessive Parkinson's disease (PD). Through the phosphorylation of its downstream targets...
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Biochem Soc Trans (2015) 43 (2): 302–307.
Published: 07 April 2015
...Aleksandar Rakovic; Philip Seibler; Christine Klein Parkinson disease (PD) is a degenerative disorder of the central nervous system resulting from depletion of dopaminergic neurons and currently remains incurable despite enormous international research efforts. The development of induced...
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Biochem Soc Trans (2014) 42 (6): 1762–1767.
Published: 17 November 2014
... to the formation of inclusions as clinical symptoms. The co-enrichment and co-localization of TPPP/p25 and α-synuclein were established in human-brain inclusions characteristic of Parkinson's disease (PD) and other synucleinopathies. The binding segments on TPPP/p25 involved in the physiological...
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Biochem Soc Trans (2014) 42 (5): 1291–1301.
Published: 18 September 2014
... 2014 Biochemical Society 2014 Alzheimer’s disease amyotrophic lateral sclerosis glia Huntington’s disease neurodegeneration Parkinson’s disease At the later stages of ALS, reactive astrogliosis also comes to the fore, as well as the activation of microglial cells [ 53 , 58...
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Biochem Soc Trans (2013) 41 (6): 1513–1517.
Published: 20 November 2013
...David R. Brown Many proteins associated with neurodegenerative diseases have poorly defined or unknown functions. α-Synuclein is one such protein which is associated with a range of diseases including Parkinson's disease. Now accepted as a metal-binding protein, α-synuclein's function could...
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Biochem Soc Trans (2012) 40 (5): 1039–1041.
Published: 19 September 2012
...Patrick A. Lewis; Dario R. Alessi LRRK2 (leucine-rich repeat kinase 2) is a gene of unknown function that has been linked to a number a human diseases, including PD (Parkinson's disease), IBD (inflammatory bowel disease), leprosy and cancer. The papers from the LRRK2: Function and Dysfunction...
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Biochem Soc Trans (2012) 40 (5): 1042–1046.
Published: 19 September 2012
...Youren Tong; Jie Shen Mutations in LRRK2 (leucine-rich repeat kinase 2) are the most common genetic cause of PD (Parkinson's disease). To investigate how mutations in LRRK2 cause PD, we generated LRRK2 mutant mice either lacking its expression or expressing the R1441C mutant form. Homozygous R1441C...
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Biochem Soc Trans (2012) 40 (5): 1152–1157.
Published: 19 September 2012
... previously inaccessible. In the case of PD (Parkinson's disease), reprogramming is advancing rapidly, and cell lines have been generated from patients carrying mutations in several disease-associated genes, including SNCA (α-synuclein), PARK2 (parkin), PINK1 (phosphatase and tensin homologue deleted...
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Biochem Soc Trans (2012) 40 (5): 1063–1069.
Published: 19 September 2012
... proteins) subfamily. Studies with recombinant LRRK2 protein purified from eukaryotic cells have confirmed that LRRK2 binds guanine nucleotides and catalyses the hydrolysis of GTP to GDP. LRRK2 is linked to PD (Parkinson's disease) and GTPase activity is impaired for several PD mutants located in the ROC...
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Biochem Soc Trans (2012) 40 (5): 1111–1116.
Published: 19 September 2012
...Elisa Belluzzi; Elisa Greggio; Giovanni Piccoli PD (Parkinson's disease) is a common neurodegenerative disease clinically characterized by bradykinesia, rigidity and resting tremor. Recent studies have proposed that synaptic dysfunction, implicated in numerous studies of animal models of PD, might...
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Biochem Soc Trans (2012) 40 (5): 1158–1162.
Published: 19 September 2012
...Jing Zhao; Spencer B. Hermanson; Coby B. Carlson; Steven M. Riddle; Kurt W. Vogel; Kun Bi; R. Jeremy Nichols Mutations in LRRK2 (leucine-rich repeat kinase 2) have been linked to inherited forms of PD (Parkinson's disease). Substantial pre-clinical research and drug discovery efforts have focused...
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Biochem Soc Trans (2012) 40 (5): 1134–1139.
Published: 19 September 2012
...Nicolas Dzamko; Glenda M. Halliday Missense mutations in LRRK2 (leucine-rich repeat kinase 2) contribute significantly to autosomal dominant PD (Parkinson's disease). Genome-wide association studies have suggested further that mutations in LRRK2 comprise a risk factor for sporadic PD. How LRRK2...
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Biochem Soc Trans (2012) 40 (5): 1070–1073.
Published: 19 September 2012
...Mark R. Cookson Mutations in LRRK2 (leucine-rich repeat kinase 2) are a relatively common cause of inherited PD (Parkinson's disease), but the mechanism(s) by which mutations lead to disease are poorly understood. In the present paper, I discuss what is known about LRRK2 in cellular models...
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Biochem Soc Trans (2012) 40 (5): 1090–1094.
Published: 19 September 2012
... pathologies including cancer and PD (Parkinson's disease). Despite an increasing research focus on these proteins, their functions in general, and their specific roles in disease, are still unknown. In the case of MASL1 (malignant fibrous histiocytoma amplified sequences with leucine-rich tandem repeats 1...
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Biochem Soc Trans (2012) 40 (5): 1140–1146.
Published: 19 September 2012
...Patricia Gómez-Suaga; Grant C. Churchill; Sandip Patel; Sabine Hilfiker Mutations in LRRK2 (leucine-rich repeat kinase 2) represent a significant component of both sporadic and familial PD (Parkinson's disease). Pathogenic mutations cluster in the enzymatic domains of LRRK2, and kinase activity...
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Biochem Soc Trans (2012) 40 (5): 1095–1101.
Published: 19 September 2012
...Laura Civiero; Luigi Bubacco Mutations in LRRK2 (leucine-rich repeat kinase 2) are associated with both familial and sporadic PD (Parkinson's disease). LRRK1 (leucine-rich repeat kinase 1) shares a similar domain structure with LRRK2, but it is not linked to PD. LRRK proteins belong to a gene...
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Biochem Soc Trans (2012) 40 (5): 1074–1079.
Published: 19 September 2012
...Yulan Xiong; Valina L. Dawson; Ted M. Dawson Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene are the most frequent genetic cause of PD (Parkinson's disease), and these mutations play important roles in sporadic PD. The LRRK2 protein contains GTPase and kinase domains and several protein...
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Biochem Soc Trans (2012) 40 (5): 1123–1128.
Published: 19 September 2012
...Daniel C. Berwick; Kirsten Harvey PD (Parkinson's disease) is a devastating progressive motor disorder with no available cure. Over the last two decades, an increasing number of genetic defects have been found that cause familial and idiopathic forms of PD. In parallel, the importance of Wnt...
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Biochem Soc Trans (2012) 40 (5): 1147–1151.
Published: 19 September 2012
...Claudia Manzoni LRRK2 (leucine-rich repeat kinase 2) is an enzyme implicated in human disease, containing kinase and GTPase functions within the same multidomain open reading frame. Dominant mutations in the LRRK2 gene are the most common cause of familial PD (Parkinson's disease). Additionally...