Article
Clinical Neurology
Jonggeol J. Kim, Mary B. Makarious, Sara Bandres-Ciga, Jesse Raphael Gibbs, Jinhui Ding, Dena G. Hernandez, Janet Brooks, Francis P. Grenn, Hirotaka Iwaki, Andrew B. Singleton, Mike A. Nalls, Cornelis Blauwendraat
Summary: This article presents the Parkinson's Disease Sequencing Browser, a Shiny-based web application that provides comprehensive summary-level frequency data from multiple large-scale genotyping and sequencing projects. Researchers can easily search for PD risk genes and variant candidates on this browser.
MOVEMENT DISORDERS
(2021)
Article
Pharmacology & Pharmacy
Snjezana Cuzic, Maja Antolic, Anja Ognjenovic, Darija Stupin-Polancec, Adriana Petrinic Grba, Boska Hrvacic, Miroslava Dominis Kramaric, Sanja Musladin, Lidija Pozgaj, Ivo Zlatar, Denis Polancec, Gorana Aralica, Marko Banic, Marija Urek, Brankica Mijandrusic Sincic, Aleksandar Cubranic, Ines Glojnaric, Martina Bosnar, Vesna Erakovic Haber
Summary: This study explored the expression of claudins in human disease and two different animal models of IBD. The diverse alterations in claudin expression by epithelial and inflammatory cells were recorded in IBD and both animal models. The results suggest that claudins are not exclusively expressed by epithelial cells, and changes in claudin mRNA levels should be interpreted in the context of overall tissue alterations.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lukasz M. Milanowski, Xu Hou, Jenny M. Bredenberg, Fabienne C. Fiesel, Liam T. Cocker, Alexandra Soto-Beasley, Ronald L. Walton, Audrey J. Strongosky, Ayman H. Faroqi, Maria Barcikowska, Magdalena Boczarska-Jedynak, Jaroslaw Dulski, Lyuda Fedoryshyn, Piotr Janik, Anna Potulska-Chromik, Katherine Karpinsky, Anna Krygowska-Wajs, Tim Lynch, Diana A. Olszewska, Grzegorz Opala, Aleksander Pulyk, Irena Rektorova, Yanosh Sanotsky, Joanna Siuda, Mariusz Widlak, Jaroslaw Slawek, Monika Rudzinska-Bar, Ryan Uitti, Monika Figura, Stanislaw Szlufik, Sylwia Rzonca-Niewczas, Elzbieta Podgorska, Pamela J. McLean, Dariusz Koziorowski, Owen A. Ross, Dorota Hoffman-Zacharska, Wolfdieter Springer, Zbigniew K. Wszolek
Summary: This study identified a potential genetic cause of Parkinson's disease in two affected siblings. However, functional analysis of patient-derived fibroblasts did not reveal significant changes, suggesting that the CTSB gene may harbor variants with different penetrance that can determine disease risk.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Sevilay Goktas Sahoglu, Yusuf Enes Kazci, Erkan Tuncay, Tugce Torun, Celal Akdeniz, Volkan Tuzcu, Esra Cagavi
Summary: This study investigated the influence of an SCN5A gene variant on tachycardia phenotype by analyzing patient-specific iPSCs and cardiomyocytes. The findings revealed a novel pathogenic SCN5A variant associated with altered Na+ channel kinetics, potentially leading to high excitability and tachycardia phenotype. The patient-derived iPSC-CM model recapitulated clinically relevant characteristics of tachycardia, offering insight into the underlying mechanisms.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Viktor Vedelek, Balazs Vedelek, Peter Lorincz, Gabor Juhasz, Rita Sinka
Summary: This study reveals functional differences between the testis-specific glutamate dehydrogenase Bb8 and the housekeeping Gdh, providing further evidence for their potential convergence in molecular evolution. Additionally, the study highlights the importance of glutamate metabolism in sperm development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Carolin Gabbert, Susen Schaake, Theresa Lueth, Christoph Much, Christine Klein, Jan O. Aasly, Matthew J. Farrer, Joanne Trinh
Summary: This study utilized Oxford Nanopore sequencing to determine the frequency and pathogenicity of GBA1 variants in Norwegian Parkinson's disease patients and controls. The findings showed that the NGMLR/Minimap2-BCFtools pipeline had the highest accuracy for variant calls. Thirteen rare GBA1 variants were identified, with two predicted to be (likely) pathogenic. Parkinson's disease patients were found to have a 4.11 times higher odds of carrying the common GBA1 variants compared to controls.
Article
Pharmacology & Pharmacy
Merav Tauber, Yair Ben-Chaim
Summary: This study found that a genetic polymorphism in the 5-HT1A receptor gene may lead to abnormal function of the receptor, providing further insight into the voltage dependence mechanism and suggesting a functional explanation for its possible link to brain pathologies.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jay S. S. Schneider
Summary: Parkinson's disease is a progressive neurodegenerative disorder impacting millions of patients worldwide. While there are treatments available for symptoms, there is no proven therapy to slow or halt disease progression. The failure of disease-modifying agents in clinical trials can be attributed to factors such as patient selection and trial design. Additionally, treatment choices have not adequately addressed the multiple and complex pathogenic mechanisms involved in Parkinson's disease. This paper suggests that using multi-functional therapeutics, such as GM1 ganglioside, which target multiple pathogenic mechanisms, may be a promising alternative strategy for success.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Amanda L. L. Woerman, Gueltekin Tamgueney
Summary: In several neurodegenerative disorders, misfolded proteins can induce additional misfolding and propagate through the central nervous system via a self-templating mechanism. Parkinson's disease patients can be subcategorized based on the origin of misfolded alpha-synuclein, either in the brain or the gut. This review discusses the role of the gut in the pathogenesis of Parkinson's disease and other neurodegenerative disorders.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Geriatrics & Gerontology
Ye Tian, Mingyang He, Lina Pan, Xin Yuan, Min Xiong, Lanxia Meng, Zhaohui Yao, Zhui Yu, Keqiang Ye, Zhentao Zhang
Summary: Parkinson's disease (PD) is a common neurodegenerative disorder with unclear cellular and molecular mechanisms, lacking appropriate animal models mimicking its pathogenesis. The newly designed N103 mouse model exhibits PD-like features, including pathological protein accumulation, neuron loss, and behavioral impairments. Transcriptomics analysis suggests that this mouse model may offer new insights into PD research.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Clinical Neurology
Chunyu Li, Junyu Lin, Qirui Jiang, Huifang Shang
Summary: A potential cause of parkinsonism, p.Glu1121Ter in PLXNA1, was identified recently. However, no further replication has been conducted in a wider range of Parkinson's disease (PD) cohorts. Our study evaluated the genetic role of PLXNA1 in PD by analyzing rare protein-coding variants in patients and healthy controls, finding enrichment of ultra-rare variants of PLXNA1 in PD and observing worsened motor symptoms in patients carrying specific variants.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Neurosciences
Wolfgang P. Ruf, Annette Palmer, Lena Doerfer, Diana Wiesner, Eva Buck, Veselin Grozdanov, Jan Kassubek, Leda Dimou, Albert C. Ludolph, Markus Huber-Lang, Karin M. Danzer
Summary: This study provides evidence that physical trauma is associated with increased asyn oligomerization in a PD mouse model, highlighting the relevance of PD pathogenesis under traumatic settings.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Genetics & Heredity
Charli E. Harlow, Josan Gandawijaya, Rosemary A. Bamford, Emily-Rose Martin, Andrew R. Wood, Peter J. van der Most, Toshiko Tanaka, Hampton L. Leonard, Amy S. Etheridge, Federico Innocenti, Robin N. Beaumont, Jessica Tyrrell, Mike A. Nalls, Eleanor M. Simonsick, Pranav S. Garimella, Eric J. Shiroma, Niek Verweij, Peter Meer, Ron T. Gansevoort, Harold Snieder, Paul J. Gallins, Dereje D. Jima, Fred Wright, Yi-hui Zhou, Luigi Ferrucci, Stefania Bandinelli, Dena G. Hernandez, Pim van der Harst, Vickas V. Patel, Dawn M. Waterworth, Audrey Y. Chu, Asami Oguro-Ando, Timothy M. Frayling
Summary: By studying genetic variants and performing functional validation, we identified a variant in the EPO gene promoter region associated with EPO levels. Using genetic prediction and large-scale genome-wide association data, we found no significant evidence of increased risk of coronary artery disease, myocardial infarction, or stroke with genetically predicted long-term rises in EPO.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Kensuke Daida, Manabu Funayama, Kimberley J. Billingsley, Laksh Malik, Abigail Miano-Burkhardt, Hampton L. Leonard, Mary B. Makarious, Hirotaka Iwaki, Jinhui Ding, J. Raphael Gibbs, Mayu Ishiguro, Hiroyo Yoshino, Kotaro Ogaki, Genko Oyama, Kenya Nishioka, Risa Nonaka, Wado Akamatsu, Cornelis Blauwendraat, Nobutaka Hattori
Summary: This study identified a large novel 7 Mb inversion involving PRKN, which is associated with young-onset Parkinson's disease. Long-read sequencing proved to be valuable for detecting complex structural variants in unresolved PD cases. The findings highlight the importance of investigating structural variants in PRKN using advanced sequencing technologies.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Rafael Rodriguez-Rojas, Jose A. Pineda-Pardo, Jorge Manez-Miro, Alicia Sanchez-Turel, Raul Martinez-Fernandez, Marta del Alamo, Mahlon DeLong, Jose A. Obeso
Summary: This study aimed to characterize the functional organization of the subthalamic nucleus (STN) and its correlation with motor outcomes induced by subthalamotomy. Results showed a gradient of connections to sensorimotor, supplementary-motor, associative, and limbic cortical regions within the STN, with overlapping zones. The study supported an interplay between segregation and integration of cortico-subthalamic projections, suggesting the coexistence of parallel and convergent information processing.
MOVEMENT DISORDERS
(2022)
Article
Pharmacology & Pharmacy
Wenlong Zhang, Xiuping Zhang, Shaogang Qu
MOLECULAR PHARMACOLOGY
(2018)
Article
Pharmacology & Pharmacy
Wenlong Zhang, Xiuping Zhang, Shaogang Qu
MOLECULAR PHARMACOLOGY
(2019)
Article
Chemistry, Multidisciplinary
Wenlong Zhang, Huaqing Chen, Liuyan Ding, Junwei Gong, Mengran Zhang, Wenyuan Guo, Pingyi Xu, Shiying Li, Yunlong Zhang
Summary: In this study, a Trojan horse system was used for targeted delivery of a blood brain barrier-penetrating peptide (RVG29) conjugated to nanoparticles loaded with the natural autophagy inducer 4,4 '-dimethoxychalcone (DMC) for the treatment of Parkinson's disease. The neuroprotective effects of DMC were demonstrated, showing improvement in motor deficits and nigral DA neuron death in PD mice without causing adverse effects. rvanism by using RVG-nDMC provides a potentially effective approach for intervention against Parkinson's disease.
Article
Biochemistry & Molecular Biology
Junwei Gong, Wenlong Zhang, Liuyan Ding, Mengran Zhang, Shaohui Zheng, Runfang Ma, Junyuan Tang, Wei Yi, Huaxi Xu, Yunlong Zhang
Summary: DMC attenuated motor impairment, degeneration of DA neurons, and alpha-synuclein aggregation in PD mouse models by increasing the expression of the riboflavin metabolic product, FMN. The restoration of redox homeostasis by DMC was mediated via the activation of PKCθ signaling.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Medicine, Research & Experimental
Wenlong Zhang, Miaomiao Zhou, Weiye Lu, Junwei Gong, Feng Gao, Yuanquan Li, Xuandong Xu, Yuwan Lin, Xiaokang Zhang, Liuyan Ding, Zhiling Zhang, Guihua Li, Xiang Chen, Xiangdong Sun, Xiaoqin Zhu, Pingyi Xu, Yunlong Zhang