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
Clinical Neurology
Sandeep Grover, Ashwin Ashok Kumar-Sreelatha, Dheeraj R. Bobbili, Patrick May, Cloe Domenighetti, Pierre-Emmanuel Sugier, Claudia Schulte, Alexis Elbaz, Rejko Kruger, Thomas Gasser, Manu Sharma
Summary: The study aimed to investigate the contribution of SV2C and WBSCR17 loci to the risk of developing PD in European and East Asian populations. The findings confirmed the role of the SV2C variant in PD pathogenesis, while the WBSCR17 rs9638616 was observed as a significant risk marker in the East Asian population only.
MOVEMENT DISORDERS
(2021)
Article
Neurosciences
G. Carola, D. Malagarriga, C. Calatayud, M. Pons-Espinal, L. Blasco-Agell, Y. Richaud-Patin, I. Fernandez-Carasa, V. Baruffi, S. Beltramone, E. Molina, P. Dell'Era, J. J. Toledo-Aral, E. Tolosa, A. R. Muotri, J. Garcia Ojalvo, J. Soriano, A. Raya, A. Consiglio
Summary: This study reveals that early dysfunction in neuronal networks in Parkinson’s disease may initiate downstream degenerative pathways before dopamine neuron loss, providing a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases.
NPJ PARKINSONS DISEASE
(2021)
Article
Cell Biology
Jonas Walter, Silvia Bolognin, Suresh K. Poovathingal, Stefano Magni, Deborah Gerard, Paul M. A. Antony, Sarah L. Nickels, Luis Salamanca, Emanuel Berger, Lisa M. Smits, Kamil Grzyb, Rita Perfeito, Fredrik Hoel, Xiaobing Qing, Jochen Ohnmacht, Michele Bertacchi, Javier Jarazo, Tomasz Ignac, Anna S. Monzel, Laura Gonzalez-Cano, Rejko Krueger, Thomas Sauter, Michele Studer, Luis Pereira de Almeida, Karl J. Tronstad, Lasse Sinkkonen, Alexander Skupin, Jens C. Schwamborn
Summary: Research has shown that the LRRK2-G2019S mutation associated with Parkinson's disease accelerates the differentiation of dopaminergic neurons, leading to an increase in cell death. The key transcription factor NR2F1 plays a role in this pathogenic mechanism by regulating the dynamics of dopaminergic differentiation.
Article
Neurosciences
Marta Soto, Manel Fernandez, Paloma Bravo, Sara Lahoz, Alicia Garrido, Antonio Sanchez-Rodriguez, Maria Rivera-Sanchez, Maria Sierra, Paula Melon, Ana Roig-Garcia, Anna Naito, Bradford Casey, Jordi Camps, Eduardo Tolosa, Maria-Jose Marti, Jon Infante, Mario Ezquerra, Ruben Fernandez-Santiago
Summary: The LRRK2 G2019S mutation is associated with Parkinson's disease, but its penetrance is not complete. By longitudinally assessing miRNA expression in serum samples from individuals with the G2019S mutation who have not developed PD symptoms, the researchers identified potential biomarkers for premotor stages of PD. They also found miRNAs that have the potential to be early progression biomarkers for PD.
NPJ PARKINSONS DISEASE
(2023)
Article
Neurosciences
Judit Pallos, Sophia Jeng, Shannon McWeeney, Ian Martin
Summary: LRRK2 mutations are the most common genetic cause of late-onset Parkinson's disease, enhancing kinase activity and causing neurodegeneration. Using TRAP and RNA-seq, researchers profiled gene expression changes specifically in dopamine neurons induced by LRRK2 G2019S in Drosophila, uncovering a range of differentially expressed genes.
NEUROBIOLOGY OF DISEASE
(2021)
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
Biology
Aurelie de Rus Jacquet, Jenna L. Tancredi, Andrew L. Lemire, Michael C. DeSantis, Wei-Ping Li, Erin K. O'Shea
Summary: This study focused on the effects of a Parkinson's disease-related mutation on astrocytes and neurons, revealing alterations in extracellular vesicle biogenesis and abnormal accumulation of PD-related proteins. The findings suggest that dysfunctional astrocyte-to-neuron communication via altered EV biological properties may participate in the progression of Parkinson's disease.
Article
Neurosciences
Olga Skiteva, Ning Yao, Ioannis Mantas, Xiaoqun Zhang, Thomas Perlmann, Per Svenningsson, Karima Chergui
Summary: In Parkinson's disease (PD), degeneration of dopaminergic (DA) neurons occurs in the substantia nigra pars compacta (SNc). This study investigated the function of voltage-gated calcium channels (VGCCs) in two different mouse models of PD. The findings revealed opposite changes in the contribution of T-type and L-type VGCCs in DA neuron somata, potentially linked to oxidative stress.
NPJ PARKINSONS DISEASE
(2023)
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
Biochemistry & Molecular Biology
Dong-Yan Song, Lin Yuan, Na Cui, Cong Feng, Lanxia Meng, Xin-He Wang, Man Xiang, Di Liu, Chun Wang, Zhentao Zhang, Jia-Yi Li, Wen Li
Summary: Parkinson's disease is an age-related chronic neurological disorder characterized by the aggregation of alpha-synuclein. This study found that over-expression of human alpha-synuclein disrupts synaptic function by interfering with vesicle recycling, but this damage can be alleviated by the re-availment of SYNJ1.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Geriatrics & Gerontology
Xuanxiang Jin, Xiaoli Si, Xiaoguang Lei, Huifang Liu, Anwen Shao, Lingfei Li
Summary: This review discusses the selectivity of vestigial dopaminergic cells in Parkinson's disease for a sub-class of hypersensitive neurons. It describes the constitution of presynaptic vesicle related to dopamine homeostasis and the genetic and environmental evidence of presynaptic dysfunction that increases the risk of Parkinson's disease. Alterations in synaptic vesicular proteins may contribute to the vulnerability of certain dopamine neurons to neurodegenerative changes.
Article
Biochemistry & Molecular Biology
Giacomo Sitzia, Olga Skiteva, Karima Chergui
Summary: The study found that the neurophysiological and synaptic characteristics of LRRK2-G2019S mice remain largely unchanged, with subtle alterations in firing patterns and glutamatergic synaptic transmission in SNr neurons, indicating changes that occur before neurodegeneration in a late-onset PD model.
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
Biology
Yu-En Lin, Chin-Hsien Lin, En-Peng Ho, Yi-Ci Ke, Stavroula Petridi, Christopher J. H. Elliott, Lee-Yan Sheen, Cheng-Ting Chien
Summary: The water extracts of Gastrodia elata Blume (GE) show neuroprotective effects in G2019S-induced Parkinson's disease fruit flies and transgenic mice by improving motor abilities and protecting dopaminergic neurons. The mechanism involves the activation of the Nrf2 protein in glial cells, which inhibits degenerative signaling pathways in neurons, ultimately preventing neuronal loss and maintaining coordination.
Article
Cell Biology
Zhiqiang Deng, Junghyun Lim, Qian Wang, Kerry Purtell, Shuai Wu, Gloria M. Palomo, Haiyan Tan, Giovanni Manfredi, Yanxiang Zhao, Junmin Peng, Bo Hu, Shi Chen, Zhenyu Yue
Article
Neurosciences
Ghazaleh Ashrafi, Jaime de Juan-Sanz, Ryan J. Farrell, Timothy A. Ryan
Article
Multidisciplinary Sciences
Insup Choi, Yuanxi Zhang, Steven P. Seegobin, Mathilde Pruvost, Qian Wang, Kerry Purtell, Bin Zhang, Zhenyu Yue
NATURE COMMUNICATIONS
(2020)
Article
Neurosciences
Kristina K. Deonaraine, Qian Wang, Haoxiang Cheng, Kenny L. Chan, Hsiao-Yun Lin, Kalena Liu, Lyonna F. Parise, Flurin Cathomas, Katherine B. Leclair, Meghan E. Flanigan, Long Li, Hossein Aleyasin, Christopher Guevara, Ke Hao, Bin Zhang, Scott J. Russo, Jun Wang
JOURNAL OF NEUROSCIENCE RESEARCH
(2020)
Article
Neurosciences
Minghui Wang, Aiqun Li, Michiko Sekiya, Noam D. Beckmann, Xiuming Quan, Nadine Schrode, Michael B. Fernando, Alex Yu, Li Zhu, Jiqing Cao, Liwei Lyu, Emrin Horgusluoglu, Qian Wang, Lei Guo, Yuan-Shuo Wang, Ryan Neff, Won-Min Song, Erming Wang, Qi Shen, Xianxiao Zhou, Chen Ming, Seok-Man Ho, Sezen Vatansever, H. Umit Kaniskan, Jian Jin, Ming-Ming Zhou, Kanae Ando, Lap Ho, Paul A. Slesinger, Zhenyu Yue, Jun Zhu, Pavel Katsel, Sam Gandy, Michelle E. Ehrlich, Valentina Fossati, Scott Noggle, Dongming Cai, Vahram Haroutunian, Koichi M. Iijima, Eric Schadt, Kristen J. Brennand, Bin Zhang
Summary: This study identified neuronal gene subnetworks as the most dysregulated in late-onset Alzheimer's Disease, with ATP6V1A as a key regulator that can improve neuronal impairment caused by LOAD through a repositioned compound, NCH-51. The detailed signaling circuits of complex molecular interactions in key brain regions affected by LOAD provide a blueprint for developing next-generation therapeutic agents against the disease.
Article
Multidisciplinary Sciences
Ryan A. Neff, Minghui Wang, Sezen Vatansever, Lei Guo, Chen Ming, Qian Wang, Erming Wang, Emrin Horgusluoglu-Moloch, Won-min Song, Aiqun Li, Emilie L. Castranio, T. C. W. Julia, Lap Ho, Alison Goate, Valentina Fossati, Scott Noggle, Sam Gandy, Michelle E. Ehrlich, Pavel Katsel, Eric Schadt, Dongming Cai, Kristen J. Brennand, Vahram Haroutunian, Bin Zhang
Summary: This study identified three major molecular subtypes of Alzheimer's disease (AD) and specific driver genes through analyzing transcriptomes from multiple brain regions. The research also demonstrated that existing AD mouse models reflect some degree of subtype heterogeneity, possibly explaining the lack of alignment between successful drugs in specific mouse models and generalized human trials across all AD subtypes. Subtyping patients with AD is considered a critical step towards precision medicine for this devastating disease.
Review
Neurosciences
Qian Wang, Bin Zhang, Zhenyu Yue
Summary: Parkinson's disease is a complex neurodegenerative disorder with heterogeneous clinical symptoms, pathologies, environmental factors, and comorbidities. Molecular network approaches have been increasingly used to identify molecular pathways and drug targets for PD, aiding in predicting the functions of genetic risk factors and discovering network-based therapies for neurodegenerative diseases.
TRENDS IN NEUROSCIENCES
(2021)
Article
Multidisciplinary Sciences
Zhiqiang Deng, Xianting Li, Marian Blanca Ramirez, Kerry Purtell, Insup Choi, Jia-Hong Lu, Qin Yu, Zhenyu Yue
Summary: The study reveals that autophagy plays a critical role in protecting cells during energy crisis by regulating cell metabolism, specifically through the selective degradation of the PKA inhibitory subunit RI. This selective autophagy process activates PKA, promotes mitochondrial metabolism, and enhances cell survival under glucose deprivation conditions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Ping-Yue Pan, Justin Zhu, Asma Rizvi, Xinyu Zhu, Hikari Tanaka, Cheryl F. Dreyfus
Summary: Dysregulation of macroautophagy due to Synj1 gene deficiency leads to excessive autophagy in astrocytes, which is implicated in Parkinson's disease. The findings suggest that Synj1 plays a crucial role in regulating autophagy in astrocytes, offering a novel perspective on the mechanism of Synj1-related Parkinsonism involving astrocyte dysfunction.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Clinical Neurology
Emrin Horgusluoglu, Ryan Neff, Won-Min Song, Minghui Wang, Qian Wang, Matthias Arnold, Jan Krumsiek, Beatriz Galindo-Prieto, Chen Ming, Kwangsik Nho, Gabi Kastenmueller, Xianlin Han, Rebecca Baillie, Qi Zeng, Shea Andrews, Haoxiang Cheng, Ke Hao, Alison Goate, David A. Bennett, Andrew J. Saykin, Rima Kaddurah-Daouk, Bin Zhang
Summary: This study aims to identify AD-specific metabolomic changes and their potential upstream genetic and transcriptional regulators through an integrative systems biology framework. The findings suggest that short-chain acylcarnitines/amino acids and medium/long-chain acylcarnitines are most associated with AD clinical outcomes. Integration of gene expression data reveals ABCA1 and CPT1A are involved in regulating acylcarnitines and amino acids in AD.
ALZHEIMERS & DEMENTIA
(2022)
Review
Neurosciences
Hassaam Choudhry, Meha Aggarwal, Ping-Yue Pan
Summary: Synj1, a phosphoinositide phosphatase, plays a critical role in neurological disorders, particularly in synaptic membrane trafficking and endosomal trafficking. Mutations and variants of Synj1 associated with synaptic vesicle recycling are linked to neurodegenerative diseases. Despite advancements in understanding Synj1's structure and function, the mechanism by which it connects to disease pathogenesis remains to be fully addressed.
NEUROSCIENCE LETTERS
(2021)
Article
Multidisciplinary Sciences
Camila Pulido, Timothy A. Ryan
Summary: The brain is metabolically fragile, especially in terms of fuel availability impacting cognitive function. Synaptic vesicle pools are a major source of presynaptic energy consumption, contributing significantly to nerve terminal tolerance to fuel deprivation. This basal metabolic process arises from compensatory mechanisms within synaptic vesicles.
Article
Biology
Daniel C. Cook, Timothy A. Ryan
Summary: Control of neurotransmission efficacy is crucial for understanding brain's information processing. Presynaptic GPCRs, which can locally affect synaptic strength, have been found to inhibit voltage-gated calcium influx, contributing to complete silencing of nerve terminals. These findings suggest that neural circuits can modulate information throughput at the single synapse level by leveraging the non-linear relationship between action potential driven calcium influx and external calcium concentration.
Article
Clinical Neurology
Xiaoyan Sun, Qian Wang, Kaj Blennow, Henrik Zetterberg, Micheline McCarthy, David A. Loewenstein, Regina Vontell, Zhenyu Yue, Bin Zhang
Summary: The study reveals that NRGN expression is correlated with synaptic damage in AD and associated with dementia rating and pathological diagnosis.
ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS
(2021)
Article
Neuroimaging
Emrin Horgusluoglu-Moloch, Gaoyu Xiao, Minghui Wang, Qian Wang, Xianxiao Zhou, Kwangsik Nho, Andrew J. Saykin, Eric Schadt, Bin Zhang
NEUROIMAGE-CLINICAL
(2020)