Review
Cell Biology
Sarmistha Mahanty, Subba Rao Gangi Setty
Summary: Epidermal lamellar bodies (eLBs) are secretory organelles necessary for skin homeostasis, belonging to lysosome-related organelles (LROs) with a complex formation process related to other organelles. Disruption of the multistep biogenesis processes often occurs in skin disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Edmundo G. Vides, Ayan Adhikari, Claire Y. Chiang, Pawel Lis, Elena Purlyte, Charles Limouse, Justin L. Shumate, Elena Spinola-Lasso, Herschel S. Dhekne, Dario R. Alessi, Suzanne R. Pfeffer
Summary: Activating mutations in LRRK2 can phosphorylate a subset of Rab GTPases. LRRK2 can be recruited by Rab29 to the surface of the Golgi and phosphorylate itself and Rab substrates. The study also found that LRRK2 can bind to Rab8A and Rab10, and identified specific binding regions. Washout experiments showed that the rapid recovery of kinase activity in cells depends on the association between LRRK2 and phosphorylated Rab proteins.
Article
Cell Biology
Chao-Ying Zhao, Lin-Lin Hu, Chun-Hua Xing, Xiang Lu, Shao-Chen Sun, Yu-Xia Wei, Yan-Ping Ren
Summary: Acrylamide exposure disrupts the distribution and functions of organelles in mouse oocytes, leading to reduced developmental competence.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Narayana Yadavalli, Shawn M. Ferguson
Summary: This study reveals that LRRK2 negatively regulates lysosome degradative activity in macrophages and microglia through transcriptional mechanisms. Depletion or inhibition of LRRK2 enhances lysosomal proteolytic activity and expression of lysosomal hydrolases, while the Parkinson's disease mutant LRRK2 G2019S suppresses lysosomal degradative activity and gene expression. MiT-TFE transcription factors are identified as mediators of LRRK2-dependent control of lysosomal gene expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Cell Biology
Antoine Marchand, Alessia Sarchione, Panagiotis S. Athanasopoulos, Helene Bauderlique-Le Roy, Liesel Goveas, Romain Magnez, Matthieu Drouyer, Marco Emanuele, Franz Y. Ho, Maxime Liberelle, Patricia Melnyk, Nicolas Lebegue, Xavier Thuru, R. Jeremy Nichols, Elisa Greggio, Arjan Kortholt, Thierry Galli, Marie-Christine Chartier-Harlin, Jean-Marc Taymans
Summary: The study investigates the functional consequences of phosphorylation or dephosphorylation of the Leucine Rich Repeat Kinase 2 (LRRK2) gene, a major genetic determinant of Parkinson's disease. The results suggest that phosphorylation of LRRK2 is associated with healthy phenotypes, while dephosphorylation is associated with phenotypes associated with Parkinson's disease pathology.
Review
Genetics & Heredity
Eun-Mi Hur, Byoung Dae Lee
Summary: Parkinson's disease is a heterogeneous neurodegenerative disease characterized by the loss of dopaminergic neurons and the formation of proteinaceous inclusions. Aging is considered a major risk factor influencing the progression of PD, with common changes in cellular functions shared by aging and PD. Mutations in the LRRK2 gene are a common genetic cause of both familial and sporadic PD, and may interact with aging to contribute to PD pathologies.
Review
Clinical Neurology
Laura J. Smith, Chiao-Yin Lee, Elisa Menozzi, Anthony H. V. Schapira
Summary: Variants in the GBA1 and LRRK2 genes are common risk factors for Parkinson's disease. GBA1 is associated with lysosomal enzymes while LRRK2 affects the phosphorylation of GTPases. GBA1-related PD has earlier onset and more severe non-motor symptoms, while LRRK2-related PD has a milder disease course.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kyohei Ito, Miho Araki, Yuta Katai, Yuki Nishimura, Sota Imotani, Haruki Inoue, Genta Ito, Taisuke Tomita
Summary: Mutations in LRRK2 cause familial Parkinson's disease (PD). Overexpression of pathogenic mutant LRRK2 leads to clustering of lysosomes in the perinuclear region, dependent on its kinase activity. The phosphorylation of Rab12 by LRRK2 enhances its interaction with RILPL1, compromising intracellular lysosomal transport and suggesting a role in LRRK2-mediated PD pathogenesis.
Review
Biochemistry & Molecular Biology
Luis Bonet-Ponce, Mark R. Cookson
Summary: Protein coding mutations in LRRK2 cause familial Parkinson's disease, while noncoding variations increase the risk of sporadic PD. These mutations increase LRRK2 kinase activity, influencing intracellular membrane trafficking.
Review
Neurosciences
Yonghang Wei, Maher un Nisa Awan, Liping Bai, Jie Bai
Summary: Parkinson's disease is a chronic neurodegenerative disease associated with intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with the disease. LRRK2 regulates intracellular vesicle transport and organelle function, including Golgi and lysosome. LRRK2 phosphorylates a group of Rab GTPases, including Rab29, Rab8, and Rab10.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Jordan Follett, Matthew J. Farrer
Summary: Parkinson's disease is a common neurodegenerative disorder with unknown etiology, potentially influenced by genetic, environmental, and inflammatory factors. Genetic variability in leucine-rich repeat kinase 2 may play a role in the pathogenesis, leading to abnormal accumulation of alpha-synuclein or tau.
Review
Neurosciences
Hui-Zhi Long, Yan Cheng, Zi-Wei Zhou, Hong-Yu Luo, Dan-Dan Wen, Li-Chen Gao
Summary: Alzheimer's disease is a global neurodegenerative disease, and ferroptosis may play an important role in its pathogenesis. Cell organelles such as mitochondria, endoplasmic reticulum, lysosome, and Golgi apparatus are involved in the regulation of ferroptosis in Alzheimer's disease.
JOURNAL OF NEUROSCIENCE RESEARCH
(2022)
Article
Cell Biology
Tadayuki Komori, Tomoki Kuwahara, Tetta Fujimoto, Maria Sakurai, Ikuko Koyama-Honda, Mitsunori Fukuda, Takeshi Iwatsubo
Summary: Recent studies have identified Rab29 as a Rab protein phosphorylated by LRRK2 and found that it is also phosphorylated under lysosomal overload stress. The phosphorylation site is Ser185 and this phosphorylation is involved in counteracting lysosomal enlargement. PKCα and PKCδ are involved in this phosphorylation and control the lysosomal localization of Rab29.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Linfang Wang, Honglei Wang, Shuanglong Yi, Shiping Zhang, Margaret S. Ho
Summary: Mutations in LRRK2 play a major role in the development of Parkinson's disease. This study demonstrates that LRRK2 is involved in regulating the lysosomal pathway in glial cells, and impairment of this pathway leads to glial apoptosis and dopaminergic neurodegeneration.
Article
Pharmacology & Pharmacy
E. Maines, S. A. M. Urru, E. Burri, G. Piccoli, A. Pedrolli, A. Pasqualini, A. L. Burlina, G. Temporin
Article
Cell Biology
Lucia Carboni, Francesca Pischedda, Giovanni Piccoli, Mario Lauria, Laura Musazzi, Maurizio Popoli, Aleksander A. Mathe, Enrico Domenici
Article
Cell Biology
Julia Obergasteiger, Giulia Frapporti, Giulia Lamonaca, Sara Pizzi, Anne Picard, Alexandros A. Lavdas, Francesca Pischedda, Giovanni Piccoli, Sabine Hilfiker, Evy Lobbestael, Veerle Baekelandt, Andrew A. Hicks, Corrado Corti, Peter P. Pramstaller, Mattia Volta
CELL DEATH DISCOVERY
(2020)
Review
Biochemistry & Molecular Biology
Francesca Pischedda, Giovanni Piccoli
Summary: The missense mutations in the LRRK2 gene are a recognized cause of inherited Parkinson's disease, and LRRK2 may impact synaptic vesicles through its diverse functions in membrane trafficking. Changes in dopamine and glutamate transmission have been described upon alterations in LRRK2 related to synaptic vesicles.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemical Research Methods
Lucia Verrillo, Eleonora Mangano, Denise Drongitis, Ivan Merelli, Francesca Pischedda, Giovanni Piccoli, Clarissa Consolandi, Roberta Bordoni, Maria Giuseppina Miano
Summary: The study introduces an innovative strategy for conducting scRNASeq studies in cryopreserved primary cortical cells, demonstrating the feasibility of utilizing frozen primary cortical cells for scRNASeq experiments with satisfactory viability and RNA recovery. The results suggest that frozen primary cortical cells can be successfully employed in scRNASeq experiments, providing unprecedented flexibility in experimental procedures conducted in different locations.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Article
Chemistry, Medicinal
Giulia Assoni, Giulia Frapporti, Eleonora Colombo, Davide Gornati, Maria Dolores Perez-Carrion, Laura Polito, Pierfausto Seneci, Giovanni Piccoli, Daniela Arosio
Summary: A small set of trehalose-centered putative autophagy inducers were designed and synthesized to identify more potent autophagy inducers than free trehalose. Various compounds were tested for autophagy-inducing properties, with trehalose-bearing PEG-AuNPs showing measurable autophagy induction at a specific concentration without significant toxicity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Clinical Neurology
Francesca Pischedda, Maria Daniela Cirnaru, Luisa Ponzoni, Michele Sandre, Alice Biosa, Maria Perez Carrion, Oriano Marin, Michele Morari, Lifeng Pan, Elisa Greggio, Rina Bandopadhyay, Mariaelvina Sala, Giovanni Piccoli
Summary: The study demonstrates that the LRRK2 G2019S mutation induces aggregation of NSF, leading to accumulation of protein inclusions in Parkinson's disease. It also shows that induction of autophagy can clear NSF aggregation and improve motor and cognitive impairment in aged G2019S mice.
Article
Oncology
Giuseppe Fiorentino, Roberto Visintainer, Enrico Domenici, Mario Lauria, Luca Marchetti
Summary: Modern profiling technologies have made significant progress in precision medicine and disease management. The integration of multiple omics data types for patient classification, as demonstrated by MOUSSE, shows potential advantages in identifying meaningful phenotype groups. MOUSSE, a new unsupervised multi-omics integration tool, outperforms other algorithms in clustering patients based on survival for various cancer types and extracts relevant biological features associated with patient survival.
Article
Pharmacology & Pharmacy
Evelina Maines, Roberto Franceschi, Caterina Rizzardi, Federica Deodato, Giovanni Piccoli, Vincenza Gragnaniello, Alberto Burlina, Massimo Soffiati
Summary: Niemann-Pick disease type B is a form of acid sphingomyelinase deficiency with lipid abnormalities. Early treatment is recommended, but clinical experiences in pediatric patients are limited.
JOURNAL OF CLINICAL LIPIDOLOGY
(2022)
Meeting Abstract
Clinical Neurology
Federica Boso, Giovanni Piccoli, Bruno Giometto
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Article
Clinical Neurology
Ludovica Iovino, Veronica Giusti, Francesca Pischedda, Elena Giusto, Nicoletta Plotegher, Antonella Marte, Ilaria Battisti, Angela Di Iacovo, Algerta Marku, Giovanni Piccoli, Rina Bandopadhyay, Carla Perego, Tiziana Bonifacino, Giambattista Bonanno, Cristina Roseti, Elena Bossi, Giorgio Arrigoni, Luigi Bubacco, Elisa Greggio, Sabine Hilfiker, Laura Civiero
Summary: This study demonstrates that the pathogenic variant G2019S of leucine-rich repeat kinase 2 (LRRK2) impairs the function of Excitatory Amino Acid Transporter 2 (EAAT2), resulting in glutamate overload in the brain, which may contribute to neurodegeneration in Parkinson's disease (PD).
ACTA NEUROPATHOLOGICA
(2022)
Article
Pharmacology & Pharmacy
Giulia Frapporti, Eleonora Colombo, Hazem Ahmed, Giulia Assoni, Laura Polito, Pietro Randazzo, Daniela Arosio, Pierfausto Seneci, Giovanni Piccoli
Summary: This study focuses on the rational design and synthesis of nano-lipid-trehalose conjugates for enhanced therapeutic application. The nanoassemblies, characterized by small diameter and high stability, exhibit improved pharmacokinetic profile.
Meeting Abstract
Biochemistry & Molecular Biology
Ludovica Iovino, Veronica Giusti, Francesca Pischedda, Elena Giusto, Nicoletta Plotegher, Antonella Marte, Ilaria Battisti, Angela Di Iacovo, Algerta Marku, Giovanni Piccoli, Rina Bandopadhyay, Carla Perego, Tiziana Bonifacino, Giambattista Bonanno, Cristina Roseti, Elena Bossi, Giorgio Arrigono, Luigi Bubacco, Elisa Greggio, Sabine Hilfiker, Laura Civiero
JOURNAL OF NEUROCHEMISTRY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Giovanni Piccoli
JOURNAL OF NEUROCHEMISTRY
(2022)