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Keyword: Parkinson's disease
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Articles
Biochem Soc Trans (2019) BST20180463.
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...
Articles
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...
Articles
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...
Articles
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 on a...
Articles
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 are...
Articles
Biochem Soc Trans (2018) 46 (4): 891-909.
Published: 19 July 2018
... mitochondrial abnormalities in the two most common neurodegenerative diseases, Parkinson's disease and Alzheimer's disease. In addition, we discuss the main strategies which have been explored in these diseases to target the mitochondria for therapeutic purposes, focusing on mitochondrially targeted...
Articles
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...
Articles
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...
Articles
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...
Articles
Biochem Soc Trans (2017) 45 (1): 131-139.
Published: 15 February 2017
...Heyne Lee; William S. James; Sally A. Cowley Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are found in familial and idiopathic cases of Parkinson's disease (PD), but are also associated with immune-related disorders, notably Crohn's disease and leprosy. Although the physiological...
Articles
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 the...
Articles
Biochem Soc Trans (2017) 45 (1): 207-212.
Published: 15 February 2017
...Jean-Marc Taymans; Eugénie Mutez; Matthieu Drouyer; William Sibran; Marie-Christine Chartier-Harlin Leucine-rich repeat kinase 2 (LRRK2) is a complex signalling protein that is a key therapeutic target, particularly in Parkinson's disease (PD). In addition, there is now evidence showing that LRRK2...
Articles
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...
Articles
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...
Articles
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 to...
Articles
Biochem Soc Trans (2015) 43 (3): 390-395.
Published: 01 June 2015
...Pilar Rivero-Ríos; Patricia Gómez-Suaga; Belén Fernández; Jesús Madero-Pérez; Andrew J. Schwab; Allison D. Ebert; Sabine Hilfiker Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene comprise the most common cause of familial Parkinson's disease (PD), and variants increase the risk for...
Articles
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...
Articles
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...
Articles
Biochem Soc Trans (2015) 43 (2): 292-296.
Published: 07 April 2015
... 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...
Articles
Biochem Soc Trans (2015) 43 (2): 275-279.
Published: 07 April 2015
...Melissa Vos; Patrik Verstreken; Christine Klein Parkinson's disease (PD) is a neurodegenerative motor disorder characterized by the loss of dopaminergic neurons. This loss of dopaminergic neurons is the pathological hallmark of the disease that results in the characteristic motor syndrome...
Articles
Biochem Soc Trans (2014) 42 (6): 1762-1767.
Published: 17 November 2014
... leading 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...
Articles
Biochem Soc Trans (2014) 42 (5): 1291-1301.
Published: 18 September 2014
... Society 2014 Alzheimer’s disease amyotrophic lateral sclerosis glia Huntington’s disease neurodegeneration Parkinson’s disease Neuroglia, represented by highly heterogeneous population of non-excitable cells of ectodermal/neural (astroglia, oligodendroglia and NG-2 glia) and mesodermal...
Articles
Biochem Soc Trans (2014) 42 (2): 600-604.
Published: 20 March 2014
...M. Angela Cenci PD (Parkinson's disease) is characterized by some typical motor features that are caused by striatal dopamine depletion and respond well to dopamine-replacement therapy with L -dopa. Unfortunately, the majority of PD patients treated with L -dopa develop abnormal involuntary...
Articles
Biochem Soc Trans (2013) 41 (6): 1509-1512.
Published: 20 November 2013
...Ryan P. McGlinchey; Jennifer C. Lee Mutations in the GBA1 gene, encoding the enzyme glucocerebrosidase, cause the lysosomal storage disorder GD (Gaucher’s disease), and are associated with the development of PD (Parkinson's disease) and other Lewy body disorders. Interestingly, GBA1 variants are...
Articles
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...
Articles
Biochem Soc Trans (2013) 41 (6): 1618-1624.
Published: 20 November 2013
... trafficking of mitochondria to areas of higher energy requirements, such as synapses, where mitochondrial densities fluctuate, further highlights the importance of efficient mitochondrial dynamics in neurons. PD (Parkinson's disease) is a common progressive neurodegenerative disorder which is characterized by...
Articles
Biochem Soc Trans (2012) 40 (5): 1086-1089.
Published: 19 September 2012
... © 2012 Biochemical Society 2012 armadillo ankyrin GTPase leucine-rich repeat kinase 2 (LRRK2) Parkinson's disease WD40 In 2004, two landmark reports first identified mutations in the large multi-domain LRRK2 (leucine-rich repeat kinase 2) as causing late-onset autosomal-dominant...
Articles
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...
Articles
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...
Articles
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...
Articles
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...
Articles
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...
Articles
Biochem Soc Trans (2012) 40 (5): 1080-1085.
Published: 19 September 2012
...Maximilian Sloan; Javier Alegre-Abarrategui; Richard Wade-Martins Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene on chromosome 12 cause autosomal dominant PD (Parkinson's disease), which is indistinguishable from sporadic forms of the disease. Numerous attempts have therefore been made...
Articles
Biochem Soc Trans (2012) 40 (5): 1102-1110.
Published: 19 September 2012
...Evy Lobbestael; Veerle Baekelandt; Jean-Marc Taymans The PD (Parkinson's disease) protein LRRK2 (leucine-rich repeat kinase 2) occurs in cells as a highly phosphorylated protein, with the majority of phosphosites clustering in the region between the ankyrin repeat and leucine-rich repeat domains...
Articles
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...
Articles
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 on...
Articles
Biochem Soc Trans (2012) 40 (5): 1129-1133.
Published: 19 September 2012
...José M. Bravo-San Pedro; Rubén Gómez-Sánchez; Mireia Niso-Santano; Elisa Pizarro-Estrella; Rosa A. González-Polo; Rosa A. González-Polo; José M. Fuentes; José M. Fuentes PD (Parkinson's disease) is a neurodegenerative disorder caused by loss of dopamine-generating cells in the substantia nigra. The...
Articles
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...
Articles
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), a...
Articles
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...
Articles
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...
Articles
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...
Articles
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...
Articles
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, in...
Articles
Biochem Soc Trans (2012) 40 (5): 1058-1062.
Published: 19 September 2012
...Elisa Greggio Interest in studying the biology of LRRK2 (leucine-rich repeat kinase 2) started in 2004 when missense mutations in the LRRK2 gene were linked to an inherited form of Parkinson's disease with clinical and pathological presentation resembling the sporadic syndrome. LRRK2 is a complex...
Articles
Biochem Soc Trans (2011) 39 (4): 862-867.
Published: 20 July 2011
... results of recent studies investigating PD (Parkinson's disease) and tauopathies using BAC-transgenic mice carrying either the LRRK2 (leucine-rich repeat kinase 2), α-synuclein ( SNCA ) or MAPT (microtubule-associated protein tau) genes. In all lines, expression of the WT (wild-type) gene resulted in...
Articles
Biochem Soc Trans (2010) 38 (2): 493-497.
Published: 22 March 2010
... plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder...
Articles
Biochem Soc Trans (2010) 38 (1): 144-149.
Published: 19 January 2010
...Lih-Shen Chin; James A. Olzmann; Lian Li Understanding how cells handle and dispose of misfolded proteins is of paramount importance because protein misfolding and aggregation underlie the pathogenesis of many neurodegenerative disorders, including PD (Parkinson's disease) and Alzheimer's disease...
Articles
Biochem Soc Trans (2009) 37 (4): 692-696.
Published: 22 July 2009
...Hozefa Amijee; Jill Madine; David A. Middleton; Andrew J. Doig The aggregation of numerous peptides or proteins has been linked to the onset of disease, including Aβ (amyloid β-peptide) in AD (Alzheimer's disease), asyn (α-synuclein) in Parkinson's disease and amylin in Type 2 diabetes. Diverse...
Articles
Biochem Soc Trans (2008) 36 (6): 1299-1303.
Published: 19 November 2008
...-amyloid from the protein. PrP (prion protein) binds copper, and this appears to be necessary for its normal function and might also reduce its probability of conversion into an infectious prion. α-Synuclein, a protein associated with Parkinson's disease, also binds copper, but, in this case, it...