Review
Neurosciences
Eunice Eun Seo Chang, Philip Wing-Lok Ho, Hui-Fang Liu, Shirley Yin-Yu Pang, Chi-Ting Leung, Yasine Malki, Zoe Yuen-Kiu Choi, David Boyer Ramsden, Shu-Leong Ho
Summary: Mutations in the LRRK2 gene are common causes of Parkinson's disease and suggest that LRRK2 could be a therapeutic target. LRRK2 mutant mice models show pathological similarities to early-stage Parkinson's disease, providing important insights into the mechanisms of the disease.
TRANSLATIONAL NEURODEGENERATION
(2022)
Review
Clinical Neurology
Mattia Volta
Summary: The discovery of mutations in LRRK2 and GBA1 has provided evidence for the involvement of autophagy and lysosome pathways in Parkinson's disease. These mutations slow down the degradation of alpha-synuclein, leading to dysfunction in the neuropathology of the disease. The development of genetic rodent models holds promise for studying pathogenic processes and validating drugs.
Review
Clinical Neurology
Mattia Volta
Summary: The discovery of mutations in LRRK2 and GBA1 that are linked to Parkinson's disease provides further evidence of the involvement of autophagy and lysosomal pathways in the disease's pathology. The development of genetic rodent models for LRRK2 and GBA1 has the potential to enhance our understanding of lysosome alterations in Parkinson's disease and provide new insights. Further research is needed to exploit these rodent models in the fight against the disease.
Review
Biochemistry & Molecular Biology
Maria Dolores Perez-Carrion, Inmaculada Posadas, Javier Solera, Valentin Cena
Summary: This review summarizes the main pathological mutations in LRRK2 that contribute to Parkinson's disease and discusses the different cellular and therapeutic strategies to correct LRRK2 homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell Biology
Marijn Kuijpers, Volker Haucke
Summary: The role of macroautophagy/autophagy in neurons and the physiological substrates in healthy neurons are still largely unknown. Research has shown that loss of neuronal autophagy can affect neurotransmission and calcium homeostasis in axonal and synaptic regions.
Article
Cell Biology
Peng Lun, Tao Ji, De-Hong Wan, Xia Liu, Xiao-Dong Chen, Shuai Yu, Peng Sun
Summary: The inhibition of HOTTIP can alleviate neuronal apoptosis and microglial activation in Parkinson's disease models by modulating miR-615-3p/FOXO1.
NEURAL REGENERATION RESEARCH
(2022)
Article
Multidisciplinary Sciences
Ranjan K. Singh, Ahmed Soliman, Giambattista Guaitoli, Eliza Stoermer, Felix von Zweydorf, Thomas Dal Maso, Asmaa Oun, Laura Van Rillaer, Sven H. Schmidt, Deep Chatterjee, Joshua A. David, Els Pardon, Thomas U. Schwartz, Stefan Knapp, Eileen J. Kennedy, Jan Steyaert, Friedrich W. Herberg, Arjan Kortholt, Christian Johannes Gloeckner, Wim Versees
Summary: Mutations in the LRRK2 gene are a leading cause of Parkinson's disease, while overactivation of LRRK2 is associated with idiopathic form of the disease. Researchers have identified and characterized nanobodies that can bind to different domains of LRRK2 and inhibit or activate its activity. These nanobodies act through an allosteric inhibitor mechanism and provide potential therapeutic strategies for Parkinson's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Veronica Mutti, Giulia Carini, Alice Filippini, Stefania Castrezzati, Lorena Giugno, Massimo Gennarelli, Isabella Russo
Summary: Chronic neuroinflammation is a crucial factor in the progression of neurodegenerative diseases like Parkinson's and Alzheimer's. The gene LRRK2, which is mutated in these diseases, has been identified as a key mediator of neuroinflammation. This study further validated LRRK2 kinase inhibition as a potential therapeutic intervention for neuroinflammation in preclinical models of Alzheimer's and Parkinson's.
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)
Review
Biochemistry & Molecular Biology
Jasmin Galper, Woojin S. Kim, Nicolas Dzamko
Summary: Genetic alterations in the LRRK2 gene are a common risk factor for Parkinson's disease. LRRK2 alterations are associated with changes in lipid pathways, which can lead to cellular pathology.
Article
Clinical Neurology
Tatiana Usnich, Eva-Juliane Vollstedt, Nathalie Schell, Volha Skrahina, Xenia Bogdanovic, Hanaa Gaber, Toni M. Foerster, Andreas Heuer, Natalia Koleva-Alazeh, Ilona Csoti, Ayse Nazli Basak, Sibel Ertan, Gencer Genc, Peter Bauer, Katja Lohmann, Anne Gruenewald, Emma L. Schymanski, Joanne Trinh, Susen Schaake, Daniela Berg, Doreen Gruber, Stuart H. Isaacson, Andrea A. Kuehn, Brit Mollenhauer, David J. Pedrosa, Kathrin Reetz, Esther M. Sammler, Enza Maria Valente, Franco Valzania, Jens Volkmann, Simone Zittel, Norbert Brueggemann, Meike Kasten, Arndt Rolfs, Christine Klein
Summary: The LIPAD project aims to systematically assess clinical signs and symptoms in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls, and investigate modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data.
FRONTIERS IN NEUROLOGY
(2021)
Review
Medicine, General & Internal
Xiao-Yan Yao, Li-Na Guan, Qi Chen, Chao Ren
Summary: The pathogenesis of Parkinson's disease involves multiple factors such as heredity, environment, and ageing. Mutations in LRRK2 are recognized as risk factors and play a significant role in the degeneration of dopaminergic neurons in PD. Glial hyperactivation-mediated neuroinflammation is also involved in the development of PD.
POSTGRADUATE MEDICAL JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Yajie Zhang, Xin Sun, Youjiao Zhang, Zhengwei Kang, Lei Cai, Jianhua Ding, Ming Lu, Gang Hu
Summary: GPBAR1 plays an important role in the pathogenesis of Parkinson's disease and its activation can counteract neurodegenerative pathology and provide neuroprotection for dopaminergic neurons.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Cell Biology
Sara R. Oliveira, Pedro A. Dionisio, Maria M. Gaspar, Leonor Correia Guedes, Miguel Coelho, Mario M. Rosa, Joaquim J. Ferreira, Joana D. Amaral, Cecilia M. P. Rodrigues
Summary: The study reveals a protective role of miR-335 in experimental models of Parkinson's disease, showing its ability to combat inflammation and neurodegenerative events.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Dominika Natalia Wojewska, Arjan Kortholt
Summary: This review provides a comprehensive overview of the current state of the art, presenting recent developments and challenges in developing LRRK2 inhibitors, and discussing extensively the potential targeting strategies from the protein perspective. As currently there are three LRRK2-targeting agents in clinical trials, more developments are predicted in the upcoming years.