Review
Biochemistry & Molecular Biology
Andrea Corsi, Cristina Bombieri, Maria Teresa Valenti, Maria Grazia Romanelli
Summary: Tau microtubule-associated proteins play important roles in neurons and are associated with several neurodegenerative diseases. Recent studies have focused on understanding the regulation of Tau splicing to develop new treatment approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Serena Petry, Behnaz Nateghi, Remi Keraudren, Nicolas Sergeant, Emmanuel Planel, Sebastien S. Hebert, Isabelle St-Amour
Summary: This study investigates the alternative splicing of tau protein in HD patients and identifies abnormal splicing events in the putamen. Differences in exon 2 splicing coincide with increased tau hyperphosphorylation, aggregation, and markers of neurodegeneration, suggesting a potential biomarker or therapeutic target.
Article
Biochemistry & Molecular Biology
Thomas Weidman, Alexis A. Nagengast, Justin R. DiAngelo
Summary: The protein 9G8 plays a role in regulating metabolic homeostasis in the fat body of Drosophila, by controlling the expression and splicing of genes involved in the immune response, xenobiotic biology, protein translation, sleep, and lipid and carbohydrate metabolism. Additionally, 9G8 may regulate the genes encoding NADPH-producing enzymes to maintain metabolic homeostasis.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Csaba Weber, Melinda Sipos, Attila Paczal, Balazs Balint, Vilibald Kun, Nicolas Foloppe, Pawel Dokurno, Andrew J. Massey, David Lee Walmsley, Roderick E. Hubbard, James Murray, Karen Benwell, Thomas Edmonds, Didier Demarles, Alain Bruno, Mike Burbridge, Francisco Cruzalegui, Andras Kotschy
Summary: The kinase DYRK1A has been identified as a promising target for drug discovery, and a biaryl compound was developed through fragment screening to efficiently bind to its ATP site. Structural optimization cycles resulted in the transformation of this compound into potent and selective DYRK1A inhibitors, with a focus on fine-tuning selectivity by exploiting structural differences with DYRK2. These inhibitors demonstrated potent inhibition of DYRK1A in cell culture and in vivo, with drug-like properties and dose-dependent tumor growth inhibition in an ovarian carcinoma model.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Victor Olmos, Evrett N. Thompson, Neha Gogia, Kimberly Luttik, Vaishnavi Veeranki, Luhan Ni, Serena Sim, Kelly Chen, Diane S. Krause, Janghoo Lim
Summary: This study reveals that mutant ATAXIN-1 can lead to diverse splicing events and contribute to the pathogenesis of spinocerebellar ataxia type 1. The researchers identify Rbfox1 as a mediator of mutant ATAXIN-1's effect on misregulated alternative splicing and demonstrate that manipulation of Rbfox1 expression can modify neurodegenerative phenotypes in a Drosophila model. These findings provide valuable insights into the molecular mechanisms and potential therapeutic strategies for spinocerebellar ataxia type 1.
HUMAN MOLECULAR GENETICS
(2023)
Review
Biochemical Research Methods
Jiashu Liu, Cui-Xiang Lin, Xiaoqi Zhang, Zongxuan Li, Wenkui Huang, Jin Liu, Yuanfang Guan, Hong-Dong Li
Summary: Alternative splicing (AS), a key pathway for transcriptional regulation, has been shown to be associated with complex diseases. Computational approaches for detecting disease-associated AS events have been developed. This review discusses the metrics used for characterizing AS events quantitatively. It also reviews and discusses three types of methods for detecting disease-associated splicing events: differential splicing analysis, aberrant splicing detection, and splicing-related network analysis. Additionally, methods for detecting genetic variants that potentially regulate splicing are described. Experimental comparisons are conducted to illustrate the performance of each method. The limitations of these methods are discussed, as well as potential ways to address them. This review aims to provide a systematic understanding of computational approaches for analyzing disease-associated splicing.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Engineering, Environmental
Fuli Zheng, Yuqing Li, Fengshun Zhang, Yi Sun, Chunyan Zheng, Zhousong Luo, Yuan-Liang Wang, Michael Aschner, Hong Zheng, Liqiong Lin, Ping Cai, Wenya Shao, Zhenkun Guo, Min Zheng, Xiao Zhen Zhou, Kun Ping Lu, Siying Wu, Huangyuan Li
Summary: Cobalt is a hazardous material that decreases the expression of Pin1, leading to neurotoxicity and neurodegeneration. Cobalt also alters the substrates of Pin1, such as Tau, amyloid precursor protein, contributing to neurodegenerative changes.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Neurosciences
Shuqiang Zhang, Junjie Zhong, Lian Xu, Yue Wu, Jie Xu, Jianhua Shi, Zhikai Gu, Xiaoyu Li, Nana Jin
Summary: Dyrk1A promotes neuronal apoptosis by suppressing ASF-mediated Bcl-x splicing, and the truncated form of Dyrk1A aggravates neuronal apoptosis by inhibiting ASF-mediated Bcl-x splicing.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Carlo Condello, Jacob I. Ayers, Clifton L. Dalgard, Madhy Garcia Garcia, Brianna M. Rivera, William W. Seeley, Daniel P. Perl, Stanley B. Prusiner
Summary: The amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) of Guam is a neurodegenerative disease characterized by tau tangles, alpha-synuclein Lewy bodies, and sparse beta-amyloid plaques. The presence of tau and beta-amyloid prions was detected in ALS-PDC brain samples, but not alpha-synuclein prions. The unique molecular signature of ALS-PDC distinguishes it from Alzheimer's disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Endocrinology & Metabolism
Panyisha Wu, Moya Zhang, Nicholas J. G. Webster
Summary: Alternative RNA splicing is an important biological process that has been linked to various clinical syndromes, but its applicability to common diseases is still uncertain. This review focuses on the changes in alternative RNA splicing in fatty liver disease and the role of splicing regulation in disease progression.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease (AD) is a common neurodegenerative disease with no effective treatments. People with Down syndrome (DS) have an increased risk of AD, and DYRK1A may be a potential therapeutic target. Through studying Drosophila models, it was found that the DYRK1A inhibitor PST-001 can improve the pathological processes caused by AD and DS-associated genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Bangfu Zhu, Tom Parsons, Wenche Stensen, John S. Mjoen Svendsen, Anders Fugelli, James J. L. Hodge
Summary: Alzheimer's disease, a common neurodegenerative disease with no cure, is more prevalent in Down syndrome patients due to potential genetic factors. Research has shown that targeting DYRK1A gene with medication can reduce neurodegeneration caused by AD and DS-related genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Bangfu Zhu, Tom Parsons, Christopher Foley, Yeng Shaw, Travis Dunckley, Christopher Hulme, James J. L. Hodge
Summary: Alzheimer's disease involves the abnormal processing of APP and Tau proteins, leading to neurodegeneration. Only a small percentage of cases are familial, making prediction and treatment difficult. Down syndrome patients have a higher risk of developing AD due to genetic factors. Drosophila models with overexpression of DYRK1A showed neurodegeneration, and small molecule inhibitors of DYRK1A were effective in suppressing disease phenotypes.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Jieun Kim, Su-Jin Kim, Ha-Ram Jeong, Jin-Hee Park, Minho Moon, Hyang-Sook Hoe
Summary: This study demonstrates the therapeutic potential of varlitinib in inhibiting neuroinflammatory responses induced by LPS and tau, providing insights into the underlying mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Jayashree Kumar, Lela Lackey, Justin M. Waldern, Abhishek Dey, Anthony M. Mustoe, Kevin M. Weeks, David H. Mathews, Alain Laederach, Jonathan P. Staley
Summary: Splicing is a highly regulated process affected by multiple factors, making it challenging to predict the effects of mutations on pre-mRNA structure and function. In this study, a novel chemical probing strategy was used to visualize endogenous precursor and mature MAPT mRNA structures in cells, allowing for predictions of mutation consequences on pre-mRNA structure. Cryo-EM structures of the spliceosome were also analyzed to predict alternative splicing outcomes, achieving high accuracy. A beta-regression weighting framework incorporating splice site strength, RNA structure, and splicing regulatory elements was developed, enabling accurate prediction of the effects of known and newly discovered mutations on MAPT splicing.
Article
Biochemistry & Molecular Biology
Nana Jin, Xiaomin Yin, Jianlan Gu, Xinhua Zhang, Jianhua Shi, Wei Qian, Yuhua Ji, Maohong Cao, Xiaosong Gu, Fei Ding, Khalid Iqbal, Cheng-Xin Gong, Fei Liu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Geriatrics & Gerontology
Yixuan Wang, Riyun Yang, Jianlan Gu, Xiaomin Yin, Nana Jin, Shutao Xie, Yifan Wang, Huanhuan Chang, Wei Qian, Jianhua Shi, Khalid Iqbal, Cheng-Xin Gong, Chun Cheng, Fei Liu
NEUROBIOLOGY OF AGING
(2015)
Article
Cell Biology
Shutao Xie, Nana Jin, Jianlan Gu, Jianhua Shi, Jianming Sun, Dandan Chu, Liang Zhang, Chun-ling Dai, Jin-hua Gu, Cheng-Xin Gong, Khalid Iqbal, Fei Liu
Article
Biochemistry & Molecular Biology
Nicolas Preitner, Jie Quan, Dan W. Nowakowski, Melissa L. Hancock, Jianhua Shi, Joseph Tcherkezian, Tracy L. Young-Pearse, John G. Flanagan
Article
Biochemistry & Molecular Biology
Jianhua Shi, Shiliang Wu, Chun-ling Dai, Yi Li, Inge Grundke-Iqbal, Khalid Iqbal, Fei Liu, Cheng-Xin Gong
Article
Biochemistry & Molecular Biology
Jianlan Gu, Jianhua Shi, Shiliang Wu, Nana Jin, Wei Qian, Jianhua Zhou, Inge-Grundke Iqbal, Khalid Iqbal, Cheng-Xin Gong, Fei Liu
Article
Neurosciences
Wei Qian, Xiaomin Yin, Wen Hu, Jianhua Shi, Jianlan Gu, Inge Grundke-Iqbal, Khalid Iqbal, Cheng-Xin Gong, Fei Liu
JOURNAL OF ALZHEIMERS DISEASE
(2011)
Article
Neurosciences
Wei Qian, Nana Jin, Jianhua Shi, Xiaomin Yin, Xiaoxia Jin, Shibao Wang, Maohong Cao, Khalid Iqbal, Cheng-Xin Gong, Fei Liu
JOURNAL OF ALZHEIMERS DISEASE
(2013)
Article
Biochemistry & Molecular Biology
Jianhua Shi, Wei Qian, Xiaomin Yin, Khalid Iqbal, Inge Grundke-Iqbal, Xiaosong Gu, Fei Ding, Cheng-Xin Gong, Fei Liu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2011)
Article
Biochemistry & Molecular Biology
Xiaomin Yin, Nana Jin, Jianlan Gu, Jianhua Shi, Jianhua Zhou, Cheng-Xin Gong, Khalid Iqbal, Inge Grundke-Iqbal, Fei Liu
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Biochemistry & Molecular Biology
Chun-Ling Dai, Jianhua Shi, Yanxing Chen, Khalid Iqbal, Fei Liu, Cheng-Xin Gong
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Biochemistry & Molecular Biology
Wei Qian, Hongwei Liang, Jianhua Shi, Nana Jin, Inge Grundke-Iqbal, Khalid Iqbal, Cheng-Xin Gong, Fei Liu
NUCLEIC ACIDS RESEARCH
(2011)
Article
Multidisciplinary Sciences
Ying Liu, Xiaojing Li, Yang Yu, Jianhua Shi, Zhihou Liang, Xiaoqin Run, Yi Li, Chun-ling Dai, Inge Grundke-Iqbal, Khalid Iqbal, Fei Liu, Cheng-Xin Gong
Meeting Abstract
Biochemistry & Molecular Biology
Cheng-Xin Gong, Jianhua Shi, Jin-hua Gu, Chunling Dai, Jianlan Gu, Xiaoxia Jin, Jianming Sun, Khalid Iqbal, Fei Liu
Article
Geriatrics & Gerontology
Sarah N. Kraeutner, Cristina Rubino, Jennifer K. Ferris, Shie Rinat, Lauren Penko, Larissa Chiu, Brian Greeley, Christina B. Jones, Beverley C. Larssen, Lara A. Boyd
Summary: This study examined the age-related changes in brain function and baseline brain structure that support motor skill acquisition. The findings showed that older adults experienced decreases in functional connectivity during motor skill acquisition, while younger adults experienced increases. Additionally, regardless of age group, lower baseline microstructure in a frontoparietal tract was associated with slower motor skill acquisition.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Karen Nuytemans, Farid Rajabli, Melissa Jean-Francois, Jiji Thulaseedhara Kurup, Larry D. Adams, Takiyah D. Starks, Patrice L. Whitehead, Brian W. Kunkle, Allison Caban-Holt, Jonathan L. Haines, Michael L. Cuccaro, Jeffery M. Vance, Goldie S. Byrd, Gary W. Beecham, Christiane Reitz, Margaret A. Pericak-Vance
Summary: This study conducted genetic research on African American AD families and identified a significant linkage signal associated with AD, highlighting the importance of diverse population-level genetic data in understanding the genetic determinants of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Kazuya Suwabe, Ryuta Kuwamizu, Kazuki Hyodo, Toru Yoshikawa, Takeshi Otsuki, Asako Zempo-Miyaki, Michael A. Yassa, Hideaki Soya
Summary: Physical exercise has a positive impact on hippocampal memory decline with aging. Recent studies have shown that even light exercise can improve memory and this improvement is mediated by the ascending arousal system. This study aimed to investigate the effects of light-intensity exercise on hippocampal memory function in healthy older adults and found that pupil dilation during exercise played a role in the memory improvement.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Ajay Sood, Ana Werneck Capuano, Robert Smith Wilson, Lisa Laverne Barnes, Alifiya Kapasi, David Alan Bennett, Zoe Arvanitakis
Summary: The objective of this study was to explore the impact of metformin on cognition and brain pathology. The results showed that metformin users had slower decline in global cognition, episodic memory, and semantic memory compared to non-users. However, the relationship between metformin use and certain brain pathology remains uncertain.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Brian N. Lee, Junwen Wang, Molly A. Hall, Dokyoon Kim, Shana D. Stites, Li Shen
Summary: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. This study analyzed participants from the Alzheimer's Disease Neuroimaging Initiative and found differential associations between cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes, as well as variations between sexes. These findings suggest that sex differences may play a role in the development of AD.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Madeline R. Hale, Rebecca Langhough, Lianlian Du, Bruce P. Hermann, Carol A. Van Hulle, Margherita Carboni, Gwendlyn Kollmorgenj, Kristin E. Basche, Davide Bruno, Leah Sanson-Miles, Erin M. Jonaitis, Nathaniel A. Chin, Ozioma C. Okonkwo, Barbara B. Bendlin, Cynthia M. Carlsson, Henrik Zetterberg, Kaj Blennow, Tobey J. Betthauser, Sterling C. Johnson, Kimberly D. Mueller
Summary: This study demonstrates a relationship between cerebrospinal fluid biomarkers and the ability to recall proper names in the preclinical phase of Alzheimer's disease.
NEUROBIOLOGY OF AGING
(2024)
Article
Geriatrics & Gerontology
Thomas T. Austin, Christian L. Thomas, Ben Warren
Summary: This study investigated the effects of age on the robustness and resilience of auditory system using the desert locust. The researchers found that gene expression changes were mainly influenced by age rather than noise exposure. Both young and aged locusts were able to recover their auditory nerve function within 48 hours of noise exposure, but the recovery of transduction current magnitude was impaired in aged locusts. Key genes responsible for robustness to noise exposure in young locusts and potential candidates for compensatory mechanisms in auditory neurons of aged locusts were identified.
NEUROBIOLOGY OF AGING
(2024)