Article
Clinical Neurology
Dongling Zhang, Liche Zhou, Yuting Shi, Jun Liu, Hongjiang Wei, Qiqi Tong, Hongjian He, Tao Wu
Summary: The study found that the free water (FW) values in the posterior substantia nigra (pSN) were significantly elevated and continued to increase in asymptomatic LRRK2 G2019S mutation carriers. There was also a negative correlation between FW changes in the left pSN and striatal binding ratio (SBR) changes in the left putamen.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
S. Schootemeijer, D. Coker, J. F. Shelton, E. Chanoff, H. M. Rowbotham, S. K. L. Darweesh, B. R. Bloem, P. Cannon, N. M. de Vries
Summary: This study investigates the awareness, barriers, and motivators to exercise among individuals with and without manifest Parkinson's disease (PD) who carry the LRRK2 G2019S mutation. The results show that a high percentage of individuals are aware of the relationship between exercise and PD, but there are differences in barriers and motivators between those with and without manifest PD. Lack of motivation is the top barrier for nonmanifest PD individuals, while injury/disability is the most common barrier for manifest PD individuals. Improving body functioning is the primary motivator for both groups.
PARKINSONISM & RELATED DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Noemie Cresto, Camille Gardier, Marie-Claude Gaillard, Francesco Gubinelli, Pauline Roost, Daniela Molina, Charlene Josephine, Noelle Dufour, Gwenaelle Auregan, Martine Guillermier, Sueva Bernier, Caroline Jan, Pauline Gipchtein, Philippe Hantraye, Marie-Christine Chartier-Harlin, Gilles Bonvento, Nadja Van Camp, Jean-Marc Taymans, Karine Cambon, Geraldine Liot, Alexis-Pierre Bemelmans, Emmanuel Brouillet
Summary: The C-terminal domain of mutated LRRK2 was shown to induce neurodegeneration of dopaminergic neurons independently of its N-terminal domains and through cell-autonomous mechanisms. Mutated alpha-syn toxicity can be enhanced by the C-terminal domain of LRRK2 through cell-autonomous mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Alicia Garrido, Enrique Santamaria, Joaquin Fernandez-Irigoyen, Marta Soto, Cristina Simonet, Manel Fernandez, Donina Obiang, Eduardo Tolosa, Maria-Jose Marti, Shalini Padmanabhan, Cristina Malagelada, Mario Ezquerra, Ruben Fernandez-Santiago
Summary: This study investigated protein and phospho-protein changes related to the G2019S mutant LRRK2 and identified specific phospho-protein changes associated with disease status. The findings can help distinguish different patient groups.
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Alison Fellgett, C. Adam Middleton, Jack Munns, Chris Ugbode, David Jaciuch, Laurence G. Wilson, Sangeeta Chawla, Christopher J. H. Elliott
Summary: In Drosophila dopaminergic neurons, Rab10 is involved in some, but not all, LRRK2-induced behavioral deficits. Therefore, variations in Rab expression may contribute to susceptibility of different dopaminergic nuclei to neurodegeneration seen in people with Parkinson's disease.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Cell Biology
Yaiza Corral Nieto, Sokhna M. S. Yakhine-Diop, Paula Moreno-Cruz, Laura Manrique Garcia, Amanda Gabrielly Pereira, Jose A. Morales-Garcia, Mireia Niso-Santano, Rosa A. Gonzalez-Polo, Elisabet Uribe-Carretero, Sylvere Durand, Maria Chiara Maiuri, Marta Paredes-Barquero, Eva Alegre-Cortes, Saray Canales-Cortes, Adolfo Lopez de Munain, Jordi Perez-Tur, Ana Perez-Castillo, Guido Kroemer, Jose M. Fuentes, Jose M. Bravo-San Pedro
Summary: Using mass spectrometry, this study identified metabolic changes in the liver of mouse models of Parkinson's disease, with the aim of finding new peripheral biomarkers for diagnosis.
Article
Clinical Neurology
Jessica M. Bright, Holly J. Carlisle, Alyssa M. A. Toda, Molly Murphy, Tyler P. Molitor, Paul Wren, Kristin M. Andruska, Enchi Liu, Carrolee Barlow
Summary: The study found that a G2019S LRRK2 selective inhibitor can effectively reduce phosphorylated biomarkers of mutant G2019S LRRK2 while protecting the normal LRRK2. This precision medicine treatment paves the way for treating G2019S LRRK2 PD.
MOVEMENT DISORDERS
(2021)
Article
Clinical Neurology
Antonio Sanchez-Rodriguez, Isabel Martinez-Rodriguez, Pascual Sanchez-Juan, Maria Sierra, Isabel Gonzalez-Aramburu, Maria Rivera-Sanchez, Javier Andres-Pacheco, Angela Gutierrez-Gonzalez, Adrian Garcia-Hernandez, Jorge Madera, Manuel Delgado-Alvarado, Jon Infante
Summary: Following an 8-year follow-up, it was found that 16% of carriers of the LRRK2-G2019S mutation had converted to Parkinson's disease. PD converters had lower striatal DaT binding at baseline compared to non-converters. While DaT-SPECT imaging shows potential for monitoring the premotor stage of the disease, its ability to predict phenoconversion is limited at the individual level.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Chemistry, Medicinal
Albert W. Garofalo, Jacob Schwarz, Kerry Zobel, Claudia Beato, Silvia Bernardi, Federica Budassi, Laura Caberlotto, Peng Gao, Cristiana Griffante, Xinying Liu, Marco Migliore, Feifei Qiao, Fabio Maria Sabbatini, Anna Sava, Mingliang Zhang, Holly J. Carlisle
Summary: The G2019S variant of LRRK2 is associated with Parkinson's disease (PD) and causes an increase in kinase activity. A series of novel kinase inhibitors have been discovered that selectively inhibit the phosphorylation of LRRK2 in the mouse brain, offering potential for precision medicine in future PD therapeutics.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Clinical Neurology
Anke Van der Perren, Diego Cabezudo, Geraldine Gelders, Javier M. Peralta Ramos, Chris Van den Haute, Veerle Baekelandt, Evy Lobbestael
Summary: The development of disease-modifying therapies for Parkinson's disease faces challenges, as the relationship between LRRK2 and alpha-synuclein in the disease remains unresolved. Studies show that total loss of LRRK2 or pharmacological inhibition did not significantly impact motor deficits or dopaminergic cell loss induced by alpha-synuclein, but did affect neuroinflammation. Further research is needed to understand the connection between neuroinflammatory processes and disease progression in Parkinson's disease.
Article
Cell Biology
Barbara Calamini, Nathalie Geyer, Nathalie Huss-Braun, Annie Bernhardt, Veronique Harsany, Pierrick Rival, May Cindhuchao, Dietmar Hoffmann, Sabine Gratzer
Summary: Parkinson's disease is a fatal neurodegenerative disorder primarily caused by the degeneration of dopaminergic neurons, with mutations in LRRK2 being a common genetic cause. Researchers have developed a PD model using LUHMES cell-derived dopaminergic neurons overexpressing G2019S LRRK2, which can help study G2019S LRRK2-mediated dopaminergic dysfunction and screen for novel PD therapeutics.
DISEASE MODELS & MECHANISMS
(2021)
Review
Pharmacology & Pharmacy
Jillian H. Kluss, Patrick A. Lewis, Elisa Greggio
Summary: This review provides updates on the current status of drugs and technologies targeting LRRK2 in the treatment of PD, evaluating their efficacy and overall safety in animal models and humans.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Article
Clinical Neurology
Katherine Leaver, Aaron Viser, Brian H. Kopell, Roberto A. Ortega, Joan Miravite, Michael S. Okun, Sonya Elango, Deborah Raymond, Susan B. Bressman, Rachel Saunders-Pullman, Marta San Luciano
Summary: This study highlights the different clinical features and response to deep brain stimulation (DBS) in G2019S LRRK2-Parkinson disease (LRRK2-PD) compared to idiopathic PD (IPD). Both STN and GPi DBS targets were effective in symptom suppression for LRRK2-PD patients. Dyskinesia commonly triggered DBS surgical candidacy in LRRK2-PD patients, while medication-refractory tremor was not a common indication for surgery in this cohort.
JOURNAL OF NEUROSURGERY
(2022)
Review
Biochemistry & Molecular Biology
Ruiwei Cao, Caiping Chen, Jing Wen, Weihe Zhao, Chaojun Zhang, Longhui Sun, Liyan Yuan, Chunlei Wu, Lei Shan, Meiyang Xi, Haopeng Sun
Summary: This review provides an overview of Parkinson's disease (PD) and LRRK2, highlighting the structure, pathogenic mutations, and mechanism of LRRK2. It summarizes the development of LRRK2 inhibitors in preclinical and clinical studies. The review aims to provide insights into targeting LRRK2 for PD intervention in the future.
BIOORGANIC CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Genta Ito, Naoko Utsunomiya-Tate
Summary: Leucine-rich repeat kinase 2 (LRRK2) is a protein kinase that phosphorylates and regulates Rab proteins. Genetic mutations in LRRK2 are implicated in both familial and sporadic Parkinson's disease (PD), but the mechanism is not well understood. PD patients with LRRK2 mutations show clinical symptoms similar to typical PD, but the pathological manifestations in their brains can vary greatly. Pathogenic mutations in LRRK2 affect its function and structure, which may contribute to the differences observed in patient pathology. This review summarizes the clinical and pathological manifestations caused by LRRK2 mutations, their impact on LRRK2's molecular function and structure, and their historical background, aiming to aid researchers in understanding LRRK2-associated PD pathogenesis.
Article
Genetics & Heredity
Hampton Leonard, Cornelis Blauwendraat, Lynne Krohn, Faraz Faghri, Hirotaka Iwaki, Glen Ferguson, Aaron G. Day-Williams, David J. Stone, Andrew B. Singleton, Mike A. Nalls, Ziv Gan-Or
JOURNAL OF MEDICAL GENETICS
(2020)
Correction
Clinical Neurology
Sven J. van der Lee, Olivia J. Conway, Iris Jansen, Minerva M. Carrasquillo, Luca Kleineidam, Erik van den Akker, Isabel Hernandez, Kristel R. van Eijk, Najada Stringa, Jason A. Chen, Anna Zettergren, Till F. M. Andlauer, Monica Diez-Fairen, Javier Simon-Sanchez, Alberto Lleo, Henrik Zetterberg, Marianne Nygaard, Cornelis Blauwendraat, Jeanne E. Savage, Jonas Mengel-From, Sonia Moreno-Grau, Michael Wagner, Juan Fortea, Michael J. Keogh, Kaj Blennow, Ingmar Skoog, Manuel A. Friese, Olga Pletnikova, Miren Zulaica, Carmen Lage, Itziar de Rojas, Steffi Riedel-Heller, Ignacio Illan-Gala, Wei Wei, Bernard Jeune, Adelina Orellana, Florian Then Bergh, Xue Wang, Marc Hulsman, Nina Beker, Niccolo Tesi, Christopher M. Morris, Begona Indakoetxea, Lyduine E. Collij, Martin Scherer, Estrella Morenas-Rodriguez, James W. Ironside, Bart N. M. van Berckel, Daniel Alcolea, Heinz Wiendl, Samantha L. Strickland, Pau Pastor, Eloy Rodriguez Rodriguez, Bradley F. Boeve, Ronald C. Petersen, Tanis J. Ferman, Jay A. van Gerpen, Marcel J. T. Reinders, Ryan J. Uitti, Lluis Tarraga, Wolfgang Maier, Oriol Dols-Icardo, Amit Kawalia, Maria Carolina Dalmasso, Merce Boada, Uwe K. Zettl, Natasja M. van Schoor, Marian Beekman, Mariet Allen, Eliezer Masliah, Adolfo Lopez de Munain, Alexander Pantelyat, Zbigniew K. Wszolek, Owen A. Ross, Dennis W. Dickson, Neill R. Graff-Radford, David Knopman, Rosa Rademakers, Afina W. Lemstra, Yolande A. L. Pijnenburg, Philip Scheltens, Thomas Gasser, Patrick F. Chinnery, Bernhard Hemmer, Martijn A. Huisman, Juan Troncoso, Fermin. Moreno, Ellen A. Nohr, Thorkild I. A. Sorensen, Peter Heutink, Pascual Sanchez-Juan, Danielle Posthuma, Jordi Clarimon, Kaare Christensen, Nilufer Ertekin-Taner, Sonja W. Scholz, Alfredo Ramirez, Agustin Ruiz, Eline Slagboom, Wiesje M. van der Flier, Henne Holstege
ACTA NEUROPATHOLOGICA
(2020)
Article
Veterinary Sciences
Jolaine M. Wilson, Chelsea K. Wallace, Angela K. Brice, Leah Makaron
JOURNAL OF MEDICAL PRIMATOLOGY
(2020)
Correction
Clinical Neurology
K. M. Moore, J. Nicholas, M. Grossman
Article
Clinical Neurology
Hirotaka Iwaki, Cornelis Blauwendraat, Mary B. Makarious, Sara Bandres-Ciga, Hampton L. Leonard, J. Raphael Gibbs, Dena G. Hernandez, Sonia W. Scholz, Faraz Faghri, Mike A. Nalls, Andrew B. Singleton
MOVEMENT DISORDERS
(2020)
Article
Clinical Neurology
Suzanne Lesage, Ariane Lunati, Marion Houot, Sawssan Ben Romdhan, Fabienne Clot, Christelle Tesson, Graziella Mangone, Benjamin Le Toullec, Thomas Courtin, Kathy Larcher, Mustapha Benmahdjoub, Mohamed Arezki, Ahmed Bouhouche, Mathieu Anheim, Emmanuel Roze, Francois Viallet, Francois Tison, Emmanuel Broussolle, Murat Emre, Hasmet Hanagasi, Basar Bilgic, Meriem Tazir, Mouna Ben Djebara, Riadh Gouider, Christine Tranchant, Marie Vidailhet, Eric Le Guern, Olga Corti, Chokri Mhiri, Ebba Lohmann, Andrew Singleton, Jean-Christophe Corvol, Alexis Brice
ANNALS OF NEUROLOGY
(2020)
Article
Genetics & Heredity
Thomas Roux, Mathieu Barbier, Melanie Papin, Claire-Sophie Davoine, Sabrina Sayah, Giulia Coarelli, Perrine Charles, Cecilia Marelli, Livia Parodi, Christine Tranchant, Cyril Goizet, Stephan Klebe, Ebba Lohmann, Lionel Van Maldergen, Christine van Broeckhoven, Marie Coutelier, Christelle Tesson, Giovanni Stevanin, Charles Duyckaerts, Alexis Brice, Alexandra Durr
GENETICS IN MEDICINE
(2020)
Article
Biochemistry & Molecular Biology
Imane Smaili, Christelle Tesson, Wafa Regragui, Helene Bertrand, Mounia Rahmani, Naima Bouslam, Ali Benomar, Alexis Brice, Suzanne Lesage, Ahmed Bouhouche
Summary: Genetic studies have shown a significant genetic component in Parkinson's disease (PD), with multiple genes playing a role in its causation. Rare functional variants identified in public databases may be associated with PD, and some rare or novel mutations could contribute to the development of PD. A high percentage of patients (77%) carry rare or new variants related to PD.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Geriatrics & Gerontology
Emmeline E. Brown, Cornelis Blauwendraat, Joanne Trinh, Mie Rizig, Mike A. Nalls, Etienne Leveille, Jennifer A. Ruskey, Hallgeir Jonvik, Manuela M. X. Tan, Sara Bandres-Ciga, Sharon Hassin-Baer, Kathrin Brockmann, Jon Infante, Eduardo Tolosa, Mario Ezquerra, Sawssan Ben Romdhan, Mustapha Benmahdjoub, Mohamed Arezki, Chokri Mhiri, John Hardy, Andrew B. Singleton, Roy N. Alcalay, Thomas Gasser, Donald G. Grosset, Nigel M. Williams, Alan Pittman, Ziv Gan-Or, Ruben Fernandez-Santiago, Alexis Brice, Suzanne Lesage, Matthew Farrer, Nicholas Wood, Huw R. Morris
Summary: The LRRK2 gene is associated with rare and common risk variants for Parkinson's disease, while DNM3 and VAMP4 may also play a role in disease risk. However, more research is needed to understand the specific mechanisms involved.
NEUROBIOLOGY OF AGING
(2021)
Letter
Clinical Neurology
Christelle Tesson, Ebba Lohmann, David Devos, Helene Bertrand, Suzanne Lesage, Alexis Brice
ACTA NEUROPATHOLOGICA
(2020)
Editorial Material
Neurosciences
Thomas Courtin, Alexis Brice
ARQUIVOS DE NEURO-PSIQUIATRIA
(2021)
Article
Genetics & Heredity
Sandra Martins, Ashraf Yahia, Ines P. D. Costa, Hassab E. Siddig, Rayan Abubaker, Mahmoud Koko, Marc Corral-Juan, Antoni Matilla-Duenas, Alexis Brice, Alexandra Durr, Eric Leguern, Laura P. W. Ranum, Antonio Amorim, Liena E. O. Elsayed, Giovanni Stevanin, Jorge Sequeiros
Summary: Machado-Joseph disease (MJD/SCA3) is the most common dominant ataxia worldwide, caused by a (CAG)n expansion. This study reports the first diagnosed MJD case in Sudan, with genetic analysis revealing shared ancestry with Portuguese, Spanish, and North American families. The STR-based haplotype of the Sudanese patients is distinct, indicating a unique genetic background.
Article
Multidisciplinary Sciences
Rebecca L. Ambrose, Aaron M. Brice, Alessandro T. Caputo, Marina R. Alexander, Leon Tribolet, Yu Chih Liu, Timothy E. Adams, Andrew G. D. Bean, Cameron R. Stewart
Article
Clinical Neurology
Katrina M. Moore, Jennifer Nicholas, Murray Grossman, Corey T. McMillan, David J. Irwin, Lauren Massimo, Vivianna M. Van Deerlin, Jason D. Warren, Nick C. Fox, Martin N. Rossor, Simon Mead, Martina Bocchetta, Bradley F. Boeve, David S. Knopman, Neill R. Graff-Radford, Leah K. Forsberg, Rosa Rademakers, Zbigniew K. Wszolek, John C. van Swieten, Lize C. Jiskoot, Lieke H. Meeter, Elise G. P. Dopper, Janne M. Papma, Julie S. Snowden, Jennifer Saxon, Matthew Jones, Stuart Pickering-Brown, Isabelle Le Ber, Agnes Camuzat, Alexis Brice, Paola Caroppo, Roberta Ghidoni, Michela Pievani, Luisa Benussi, Giuliano Binetti, Bradford C. Dickerson, Diane Lucente, Samantha Krivensky, Caroline Graff, Linn Oijerstedt, Marie Fallstrom, Hakan Thonberg, Nupur Ghoshal, John C. Morris, Barbara Borroni, Alberto Benussi, Alessandro Padovani, Daniela Galimberti, Elio Scarpini, Giorgio G. Fumagalli, Ian R. Mackenzie, Ging-Yuek R. Hsiung, Pheth Sengdy, Adam L. Boxer, Howie Rosen, Joanne B. Taylor, Matthis Synofzik, Carlo Wilke, Patricia Sulzer, John R. Hodges, Glenda Halliday, John Kwok, Raquel Sanchez-Valle, Albert Llado, Sergi Borrego-Ecija, Isabel Santana, Maria Rosario Almeida, Miguel Tabuas-Pereira, Fermin Moreno, Myriam Barandiaran, Begona Indakoetxea, Johannes Levin, Adrian Danek, James B. Rowe, Thomas E. Cope, Markus Otto, Sarah Anderl-Straub, Alexandre de Mendonca, Carolina Maruta, Mario Masellis, Sandra E. Black, Philippe Couratier, Geraldine Lautrette, Edward D. Huey, Sandro Sorbi, Benedetta Nacmias, Robert Laforce, Marie-Pier L. Tremblay, Rik Vandenberghe, Philip Van Damme, Emily J. Rogalski, Sandra Weintraub, Alexander Gerhard, Chiadi U. Onyike, Simon Ducharme, Sokratis G. Papageorgiou, Adeline Su Lyn Ng, Amy Brodtmann, Elizabeth Finger, Rita Guerreiro, Jose Bras, Jonathan D. Rohrer, Carolin Heller, Rhian Convery, Ione O. C. Woollacott, Rachelle Shafei, Jonathan Graff-Radford, David T. Jones, Christina M. Dheel, Rodolfo Savica, Maria I. Lapid, Matt Baker, Julie A. Fields, Ralitza Gavrilova, Kimiko Domoto-Reilly, Jackie M. Poos, Emma L. van der Ende, Jessica L. Panman, Laura Donker Kaat, Harro Seelaar, Anna Richardson, Giovanni Frisoni, Anna Mega, Silvia Fostinelli, Huei-Hsin Chiang, Antonella Alberici, Andrea Arighi, Chiara Fenoglio, Hilary Heuer, Bruce Miller, Anna Karydas, Jamie Fong, Maria Joao Leitao, Beatriz Santiago, Diana Duro, Carlos Ferreira, Alazne Gabilondo, Maria de Arriba, Mikel Tainta, Miren Zulaica, Catarina B. Ferreira, Elisa Semler, Albert Ludolph, Bernhard Landwehrmeyer, Alexander E. Volk, Gabriel Miltenberger, Ana Verdelho, Sonia Afonso, Maria Carmela Tartaglia, Morris Freedman, Ekaterina Rogaeva, Camilla Ferrari, Irene Piaceri, Valentina Bessi, Gemma Lombardi, Frederic St-Onge, Marie-Claire Dore, Rose Bruffaerts, Mathieu Vandenbulcke, Jan Van den Stock, M. Marsel Mesulam, Eileen Bigio, Christos Koros, John Papatriantafyllou, Christos Kroupis, Leonidas Stefanis, Christen Shoesmith, Erik Roberson, Giovanni Coppola, Eliana Marisa Da Silva Ramos, Daniel Geschwind
Article
Geriatrics & Gerontology
Dick Schijven, Remi Stevelink, Mark McCormack, Wouter van Rheenen, Jurjen J. Luykx, Bobby P. C. Koeleman, Jan H. Veldink
NEUROBIOLOGY OF AGING
(2020)
Article
Clinical Neurology
Jun-Pyo Hong, Hanim Kwon, Euyhyun Park, Sun-Uk Lee, Chan-Nyoung Lee, Byung-Jo Kim, Ji-Soo Kim, Kun-Woo Park
Summary: In patients with mild-to-moderate PD, vestibular function assessed by video head-impulse tests appears relatively preserved and has minimal impact on the risk of falls. Risk of postural instability is associated with the severity of clinical symptoms in PD.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yaqin Xiang, XiuRong Huang, Qian Xu, Zhenhua Liu, Yase Chen, Qiying Sun, Junling Wang, Hong Jiang, Lu Shen, Xinxiang Yan, Beisha Tang, Jifeng Guo
Summary: Using the novel data-driven method DEBM, this study determined the sequence of several common biomarker changes in Parkinson's disease (PD). The left putamen was found to be the earliest biomarker to become abnormal, followed by the right putamen, CSF alpha-synuclein, right caudate, left caudate, and serum NfL. The estimated disease stages showed significant differences between PD and healthy controls, and achieved a high accuracy for distinguishing PD from HC.
PARKINSONISM & RELATED DISORDERS
(2024)
Article
Clinical Neurology
Yan Li, David J. McLernon, Carl E. Counsell, Angus D. Macleod
Summary: This study aimed to investigate the incidence and risk factors for institutionalisation in Parkinson's disease (PD) and atypical parkinsonism (AP). The study found that institutionalisation was more frequent in AP compared to PD and controls. Age, poorer cognition, and more-severe parkinsonian impairment were independent predictors of institutionalisation.
PARKINSONISM & RELATED DISORDERS
(2024)
