Review
Pharmacology & Pharmacy
Benjamin R. Troutwine, Laylan Hamid, Colton R. Lysaker, Taylor A. Strope, Heather M. Wilkins
Summary: Genetic variation in the APOE gene is associated with the risk of Alzheimer's disease. The APOE epsilon 4 alleles are the strongest genetic risk factor for late onset sporadic AD, while the APOE epsilon 2 alleles have lower risk and the APOE epsilon 3 alleles have neutral risk.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Cell Biology
Riho Komuro, Yuka Honda, Motoaki Yanaizu, Masami Nagahama, Yoshihiro Kino
Summary: Genetic variations of CD33, specifically the rs12459419 polymorphism on exon 2, affect its alternative splicing and have been associated with the risk of Alzheimer's disease. The minor allele promotes skipping of exon 2, resulting in a shorter CD33 isoform lacking the ligand-binding domain and reduced suppressive signaling on microglial activity. HNRNPA1 was found to promote exon 2 skipping, but simultaneous knockdown of HNRNPA1, HNRNPA2B1, and HNRNPA3 increased exon 2 inclusion, suggesting functional redundancy among these proteins.
Article
Clinical Neurology
Madia Lozupone, Bruno Pietro Imbimbo, Claudia Balducci, Filomena Lo Vecchio, Paola Bisceglia, Raffaela Rita Latino, Maurizio Leone, Vittorio Dibello, Vincenzo Solfrizzi, Antonio Greco, Antonio Daniele, Mark Watling, Davide Seripa, Francesco Panza
Summary: This article discusses the role of human apolipoprotein E (apoE) in the pathophysiology of Alzheimer's disease (AD), describing its impact on brain homeostasis, neuroinflammation, blood-brain barrier permeability, glial function, synaptogenesis, oral/gut microbiota, neural networks, amyloid beta deposition, and tau-mediated neurodegeneration. It also provides updates on different therapeutic approaches targeting apoE in AD treatment.
ALZHEIMERS & DEMENTIA
(2023)
Article
Cell Biology
Yanjun Lu, Lu Tan, Jiazhao Xie, Liming Cheng, Xiong Wang
Summary: This study revealed microglia-specific alternative splicing events in Alzheimer's disease and identified novel pathological mechanisms related to AD.
Review
Genetics & Heredity
Egle Jakubauskiene, Arvydas Kanopka
Summary: Alternative pre-mRNA splicing is essential for generating protein diversity and is implicated in the pathogenesis of neurological disorders. The splicing machinery also plays a role in cellular adaptation to different microenvironments, such as hypoxia. Understanding the alternative splicing of genes associated with Alzheimer's and Parkinson's diseases can provide insights into the development of these neurodegenerative conditions, including the influence of cellular hypoxic microenvironments.
Article
Neurosciences
Kif Liakath-Ali, Thomas C. Sudhof
Summary: This study explores the alternative splicing of the presynaptic cell-adhesion molecules Neurexins, particularly focusing on Nrxn1 at splice site 4 (SS4) and its potential link to activity-dependent synaptic plasticity. However, conflicting results and potential artifacts in common testing procedures call for more sophisticated approaches to address this important question.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
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
Chemistry, Multidisciplinary
Dylan Mah, Yanan Zhu, Guowei Su, Jing Zhao, Ashely Canning, James Gibson, Xuehong Song, Eduardo Stancanelli, Yongmei Xu, Fuming Zhang, Robert J. Linhardt, Jian Liu, Lianchun Wang, Chunyu Wang
Summary: Apolipoprotein E (ApoE)'s epsilon 4 allele is the most important genetic risk factor for late onset Alzheimer's Disease (AD). Heparan sulfate (HS) on the cell surface acts as a cofactor for the interaction between ApoE and LRP1, as well as the prion-like spread of tau pathology between cells. 3-O-sulfated HS has been linked to AD through its interaction with tau, and increased levels of 3-O-sulfated HS and 3-O-sulfotransferases have been observed in the AD brain. This study characterizes the interactions between ApoE and HS in different ApoE isoforms, and suggests that the interplay between 3-O-sulfated HS, tau, and ApoE isoforms may modulate AD risk.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Neurosciences
Alexander P. Gabrielli, Ian Weidling, Amol Ranjan, Xiaowan Wang, Lesya Novikova, Subir Roy Chowdhury, Blaise Menta, Alexandra Berkowicz, Heather M. Wilkins, Kenneth R. Peterson, Russell H. Swerdlow
Summary: Mitochondrial dysfunction can activate APOE expression by altering transcription factors and stress signaling pathways, thereby influencing the biology of the APOE gene and apoE protein.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Review
Neurosciences
Yanhui Zhang, Huiling Gao, Wei Zheng, He Xu
Summary: Alzheimer's disease is the most common type of dementia in elderly individuals, and there is currently no effective disease-modifying treatment. Imbalance in brain metal ions has been found to be closely related to the onset and progression of Alzheimer's disease. Recent evidence suggests that interactions between brain metal ions and apolipoprotein E may be one of the mechanisms for neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Genetics & Heredity
Yanjun Lu, Daoyuan Yue, Jiazhao Xie, Liming Cheng, Xiong Wang
Summary: This study systematically characterized alternative splicing changes in the cerebral cortex of APP/PS1 mice and revealed ontology-specific alterations in Alzheimer's disease. The findings provide novel insights into the pathological mechanisms of AD.
FRONTIERS IN GENETICS
(2022)
Article
Chemistry, Multidisciplinary
Shanshan Zhang, Sajid Asghar, Chenqi Zhu, Junxiu Ye, Ling Lin, Liu Xu, Ziyi Hu, Zhipeng Chen, Feng Shao, Yanyu Xiao
Summary: This study presents a multi-functional delivery system (APND-3) designed to address the issues of poor drug delivery to the brain in Alzheimer's disease (AD) treatment. The system, based on a novel peptide (MOP) with self-assembling properties, significantly enhances the delivery of MOP to the brain, reducing A beta deposition and improving neurological outcomes in AD model mice.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Geriatrics & Gerontology
Giuseppe Biamonti, Angela Amato, Elisa Belloni, Anna Di Matteo, Lucia Infantino, Davide Pradella, Claudia Ghigna
Summary: Alzheimer's disease is the most common neurodegenerative disorder in the elderly, with approximately 20% of people over 80 affected. Recent studies have shown that Alternative Splicing is involved in gene expression reprogramming and splicing abnormalities in AD tissues. While the molecular causes of AD are still poorly understood, therapeutic approaches targeting aberrant AS regulation offer potential new treatments.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2021)
Review
Clinical Neurology
Xiao-Yu Ji, Xin-Yuan Peng, Hai-Liang Tang, Hui Pan, Wei-Tang Wang, Jie Wu, Jian Chen, Nai-Li Wei
Summary: The APOE4 gene variant is the most significant genetic risk factor for Alzheimer's disease, promoting its initiation and progression. The high affinity of the APOE4 allele to triglycerides and cholesterol, leading to differences in lipid metabolism, has a widespread impact on neurons, microglia, and astrocytes. Phenotypic classification of Alzheimer's patients based on APOE4 carrier status is hypothesized to aid research, diagnosis, and treatment, as it has been found to have phenotypic differences and varied responses to treatment.
Article
Medicine, General & Internal
Elena Camporesi, Johanna Nilsson, Agathe Vrillon, Emmanuel Cognat, Claire Hourregue, Henrik Zetterberg, Kaj Blennow, Bruno Becker, Ann Brinkmalm, Claire Paquet, Gunnar Brinkmalm
Summary: The synaptic proteins NRXN and Nlgn are not suitable biomarkers for synaptic pathology in Alzheimer's disease, as they show weak correlation with core biomarkers and reflect different pathogenic processes at the synapse.
Article
Chemistry, Multidisciplinary
Hai-ying Zhang, Hui Shen, Chloe J. Jordan, Qing-rong Liu, Eliot L. Gardner, Antonello Bonci, Zheng-xiong Xi
ACTA PHARMACOLOGICA SINICA
(2019)
Article
Chemistry, Multidisciplinary
Qing-Rong Liu, Nicholas S. Huang, Hong Qu, Jennifer F. O'Connell, Isabel Gonzalez-Mariscal, Sara Santa-Cruz-Calvo, Maire E. Doyle, Zheng-Xiong Xi, Yun Wang, Emmanuel. S. Onaivi, Josephine M. Egan
ACTA PHARMACOLOGICA SINICA
(2019)
Article
Behavioral Sciences
Ana Canseco-Alba, Norman Schanz, Branden Sanabria, Juan Zhao, Zhicheng Lin, Qing-Rong Lu, Emmanuel S. Onaivi
BEHAVIOURAL BRAIN RESEARCH
(2019)
Article
Cell Biology
Stephanie Lazo, Nicole Noren Hooten, Jamal Green, Erez Eitan, Nicolle A. Mode, Qing-Rong Liu, Alan B. Zonderman, Ngozi Ezike, Mark P. Mattson, Paritosh Ghosh, Michele K. Evans
Summary: The mitochondrial free radical theory of aging posits that oxidative damage to mitochondria and mtDNA contributes to aging. This study found a portion of ccf-mtDNA in plasma is encapsulated in EVs, and that EV mtDNA levels decrease with age. Additionally, EVs from old and young donors had differential effects on mitochondrial respiration, suggesting an age-dependent impact of EVs on mitochondrial energetics.
Article
Biochemistry & Molecular Biology
Qing-Rong Liu, Ana Canseco-Alba, Ying Liang, Hiroki Ishiguro, Emmanuel S. Onaivi
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Cell Biology
Yoo Kim, Sudeep Gautam, Kanikkai Raja Aseer, Jaekwan Kim, Prabha Chandrasekaran, Caio Henrique Mazucanti, Paritosh Ghosh, Jennifer F. O'Connell, Maire E. Doyle, Ashley Appleton, Elin Lehrmann, Qing-Rong Liu, Josephine M. Egan
CELL DEATH & DISEASE
(2020)
Article
Chemistry, Multidisciplinary
Hai-Ying Zhang, Lindsay De Biase, Ramesh Chandra, Hui Shen, Qing-Rong Liu, Eliot Gardner, Mary Kay Lobo, Zheng-Xiong Xi
Summary: Cannabinoid CB2 receptors are involved in drug reward and addiction. Repeated cocaine exposure increases CB2R expression in the brain and spleen, while repeated heroin administration leads to a dose-dependent reduction in CB2 mRNA expression in the striatum. Upregulation of CB2R mainly occurs in D-1-MSNs, not in D-2-MSNs or microglia.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Pathology
Maire E. Doyle, Ashley Appleton, Qing-Rong Liu, Qin Yao, Caio H. Mazucanti, Josephine M. Egan
Summary: The study found that SARS-CoV-2 may enter the human body through infecting taste papillae cells, affecting taste receptor stem cell activity and causing taste impairment. Some patients still had not fully recovered, with disrupted taste stem cells.
AMERICAN JOURNAL OF PATHOLOGY
(2021)
Article
Endocrinology & Metabolism
Qing-Rong Liu, Min Zhu, Pingbo Zhang, Caio H. Mazucanti, Nicholas S. Huang, Doyle L. Lang, Qinghua Chen, Pavan Auluck, Stefano Marenco, Jennifer F. O'Connell, Luigi Ferrucci, Chee W. Chia, Josephine M. Egan
Summary: The human insulin gene has diverged from ancestral genes millions of years ago and recent research revealed novel isoforms and protein products. A new peptide segment named Cα-peptide was found, distinct from the conventional C-peptide. The ratio of a 74-amino acid proinsulin to proconvertase-processed Cα-peptide was significantly increased in type 2 diabetes mellitus autopsy donors, suggesting potential clinical relevance.
Review
Pharmacology & Pharmacy
Qing-Rong Liu, Kanikkai Raja Aseer, Qin Yao, Xiaoming Zhong, Paritosh Ghosh, Jennifer F. O'Connell, Josephine M. Egan
Summary: CB2R may play important roles in autoimmune diabetes by regulating inflammasomes, intracellular autophagy, and extracellular vesicle release, which in turn regulate the function of pancreatic islets.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Psychiatry
Ana Canseco-Alba, Branden Sanabria, Mariam Hammouda, Rollanda Bernadin, Marizel Mina, Qing-Rong Liu, Emmanuel S. Onaivi
Summary: DAT-Cnr2 cKO mice, which do not express CB2R in midbrain dopamine neurons, exhibit reduced hyperactivity phenotype and decreased anxiety-like behavior, but increased impulsivity and risky behavior. They also show deficient response in delay decision making and perform similarly to WT mice in attention tests. The study suggests that DAT-Cnr2 cKO mice may serve as a possible model for studying the neurobiological basis of ADHD.
FRONTIERS IN PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Qing-Rong Liu, Min Zhu, Qinghua Chen, Maja Mustapic, Dimitrios Kapogiannis, Josephine M. Egan
Summary: This study uncovered novel peptides associated with human-specific IAPP isoforms, which could serve as blood-based biomarkers for early Alzheimer's disease and be developed as peptide-based anti-amyloid medicine.
Article
Behavioral Sciences
Berhanu Geresu Kibret, Aaliyah Roberts, Adam Kneebone, Shymaa Embaby, Justin Fernandez, Qing-Rong Liu, Emmanuel S. Onaivi
Summary: The endocannabinoid system (ECS) plays an important role in modulating alcohol-induced neuroinflammation and behavioral impairments. The cannabinoid type 2 receptors (CB2Rs) have been found to be involved in regulating behavior and neuroinflammation, suggesting their potential as therapeutic targets for alcohol use disorder.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Cell Biology
Caio Henrique Mazucanti, Vernon Kennedy, Hasitha U. Premathilake, Maire E. Doyle, Jane Tian, Qing-Rong Liu, Jennifer O'Connell, Simonetta Camandola, Josephine M. Egan
Summary: The choroid plexus is an important source of insulin in the central nervous system, and its secretion is regulated by Htr2c-mediated signaling. Modulating insulin expression in the choroid plexus affects food intake, anxiety behavior, and synaptic processes in the hypothalamus. Additionally, CP-derived insulin directly acts on the hypothalamus through Gq signaling.
Article
Medicine, Research & Experimental
Caio Henrique Mazucanti, Qing-Rong Liu, Doyle Lang, Nicholas Huang, Jennifer F. O'Connell, Simonetta Camandola, Josephine M. Egan
