Review
Biochemistry & Molecular Biology
Oscar M. Munoz M. Herrera, Angela M. M. Zivkovic
Summary: Cholesterol plays a crucial role in brain function and structure, and its dysregulation has been associated with neurodegenerative diseases such as Alzheimer's disease. While the regulation and dysregulation of cholesterol metabolism and transport in neurons and astrocytes are well-studied, less is known about how microglia, the immune cells of the brain, handle cholesterol and how this affects their functions. This review discusses the role of cholesterol in regulating microglia phenotype and function, the effects of statins on microglia, and highlights areas for future research to develop novel therapies for the prevention and treatment of Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Oscar Munoz M. Herrera, Brian V. V. Hong, Ulises Ruiz Mendiola, Izumi Maezawa, Lee-Way Jin, Carlito B. Lebrilla, Danielle J. Harvey, Angela M. Zivkovic
Summary: Research has shown that specific genes in microglia are highly associated with Alzheimer's disease (AD) and microglia play a critical role in the development of AD. Therefore, microglia are an important target for novel AD treatment approaches. A study used a multi-stimulant approach to examine the human microglia cell 3 (HMC3) cell line's ability to replicate dysfunctional microglia characteristics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Yuri Mizuno, Nona Abolhassani, Guianfranco Mazzei, Takashi Saito, Takaomi C. Saido, Ryo Yamasaki, Jun-ichi Kira, Yusaku Nakabeppu
Summary: Oxidative stress is a major risk factor for Alzheimer's disease, characterized by the accumulation of 8-oxoG in the brain. Deficiency of MTH1 and OGG1 accelerates the accumulation of 8-oxoG in DNA and leads to reduced anxiety-related behavior in 6-month-old mice.
NEUROSCIENCE RESEARCH
(2022)
Review
Neurosciences
Xiaojing Bai, Meiting Mai, Kai Yao, Mengqi Zhang, Yue Huang, Wenbin Zhang, Xiaorou Guo, Yixuan Xu, Ying Zhang, Atikam Qurban, Lijie Duan, Jimei Bu, Jianfeng Zhang, Junfeng Wu, Yongfei Zhao, Xiangshan Yuan, Hengbing Zu
Summary: Based on previous studies and research on DHCR24, it is suggested that the deficiency of DHCR24 activity leading to reduced cholesterol levels in plasma membrane and intracellular compartments may be involved in the pathogenesis of Alzheimer's Disease. DHCR24 could play a crucial role in maintaining cholesterol homeostasis, and its downregulation by major risk factors for AD may have a potential link with AD pathogenesis.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Biology
Angela R. Garcia, Caleb Finch, Margaret Gatz, Thomas Kraft, Daniel Eid Rodriguez, Daniel Cummings, Mia Charifson, Kenneth Buetow, Bret A. Beheim, Hooman Allayee, Gregory S. Thomas, Jonathan Stieglitz, Michael D. Gurven, Hillard Kaplan, Benjamin C. Trumble
Summary: Genes contain instructions for cells to make proteins, with different gene variants affecting protein function and disease risk. The APOE4 gene variant increases the risk of Alzheimer's and heart disease, but may have benefits in certain contexts. Studies in industrialized countries link APOE4 to higher cholesterol and inflammation, but research in indigenous populations suggests a potential benefit in pathogen-rich environments.
Article
Clinical Neurology
Aliza P. Wingo, Selina M. Vattathil, Jiaqi Liu, Wen Fan, David J. Cutler, Allan Levey, Julie A. Schneider, David A. Bennett, Thomas S. Wingo
Summary: This study found that LDL-C is associated with various neuropathological manifestations of AD independent of APOE, suggesting that LDL-C may be a modifiable risk factor for AD.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Neurosciences
Ze-Lin Hu, Yang-Qi Yuan, Zhen Tong, Mei-Qing Liao, Shun-Ling Yuan, Ye Jian, Jia-Lun Yang, Wen-Feng Liu
Summary: Alzheimer's disease is a degenerative disease of the central nervous system. Imbalances in cholesterol homeostasis have been found in the brains of AD patients. Cholesterol deposition occurs in AD brains even without entry through the blood-brain barrier. Cholesterol metabolism in the brain is associated with various pathological conditions.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Nutrition & Dietetics
Huei-Ying Chiu, Hsin-Te Chang, Po-Chi Chan, Pai-Yi Chiu
Summary: This study conducted a retrospective analysis on post-menopausal women and found that the lowest quartile of total cholesterol levels increased the risk of developing dementia, while hormone replacement therapy did not have an impact on dementia conversion.
Article
Neurosciences
Shu-Yi Huang, Yu-Xiang Yang, Ya-Ru Zhang, Kevin Kuo, Hong-Qi Li, Xue-Ning Shen, Shi-Dong Chen, Ke-Liang Chen, Qiang Dong, Lan Tan, Jin-Tai Yu
Summary: Using a two-sample Mendelian randomization approach, this study found a causal association between circulating glycoprotein acetyls, ApoB, LDL cholesterol, and serum total cholesterol levels and a higher risk of Alzheimer's disease (AD), while increased levels of glutamine were associated with a lower risk of AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Brian Hong, Jingyuan Zheng, Joanne K. Agus, Xinyu Tang, Carlito B. Lebrilla, Lee-Way Jin, Izumi Maezawa, Kelsey Erickson, Danielle J. Harvey, Charles S. DeCarli, Dan M. Mungas, John M. Olichney, Sarah T. Farias, Angela M. Zivkovic
Summary: The study aimed to determine the influence of APOE genotype on HDL function and size in the context of Alzheimer's disease. The results showed that there were differences in HDL function and size between APOE3E3 and APOE3E4 carriers and these were associated with cognitive function in patients.
Article
Neurosciences
Meiting Mai, Xiaorou Guo, Yue Huang, Wenbin Zhang, Yixuan Xu, Ying Zhang, Xiaojing Bai, Junfeng Wu, Hengbing Zu
Summary: The deficiency of DHCR24 can lead to hyperphosphorylation of tau protein in astrocytes, which is associated with the lipid raft-dependent signaling pathway. This finding may contribute to the understanding of the pathogenesis of degenerative tauopathies such as Alzheimer's disease.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aseel El Hajj, Ameziane Herzine, Gaetano Calcagno, Frederic Desor, Fathia Djelti, Vincent Bombail, Isabelle Denis, Thierry Oster, Catherine Malaplate, Maxime Vigier, Sandra Kaminski, Lynn Pauron, Catherine Corbier, Frances T. Yen, Marie-Claire Lanhers, Thomas Claudepierre
Summary: Perturbations in cholesterol metabolism are linked to neurodegenerative diseases. The interaction between glial cells and neurons is essential for regulating brain cholesterol trafficking. The lipolysis-stimulated lipoprotein receptor (LSR) plays a crucial role in maintaining brain cholesterol homeostasis. Deficiency of astroglial LSR may result in cognitive defects and neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Na Zhan, Boyang Wang, Nikita Martens, Yankai Liu, Shangge Zhao, Gardi Voortman, Jeroen Van Rooij, Frank Leijten, Tim Vanmierlo, Folkert Kuipers, Johan W. Jonker, Vincent W. Bloks, Dieter Luetjohann, Marcella Palumbo, Francesca Zimetti, Maria Pia Adorni, Hongbing Liu, Monique T. Mulder
Summary: The study identified five novel LXR-activating 24-oxidized sterols with potential therapeutic applications in neurodegenerative and cardiovascular diseases. These compounds demonstrated high potency for LXR alpha/beta activation and induced the expression of LXR-target genes involved in cellular cholesterol turnover. They also enhanced cholesterol efflux and upregulated the production of endogenous LXR agonists. Overall, these findings suggest the potential of developing compounds targeting LXR for the treatment of lipid-related diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Nutrition & Dietetics
Laura Bonfili, Massimiliano Cuccioloni, Chunmei Gong, Valentina Cecarini, Michele Spina, Yadong Zheng, Mauro Angeletti, Anna Maria Eleuteri
Summary: This study investigated the effects of probiotics on lipid metabolism in AD mice, demonstrating that probiotic treatment can inhibit cholesterol biosynthesis, influence bile acid synthesis pathways, regulate inflammation, and improve lipid composition, with arachidonic acid playing a key role in these interactions.
CLINICAL NUTRITION
(2022)
Article
Medicine, General & Internal
Jiang-Shan Tan, Meng-Jin Hu, Yan-Min Yang, Yue-Jin Yang
Summary: This study used Mendelian randomization to explore the causal associations between LDL-C level and the risks of individual and familial Alzheimer's disease (AD). The results showed a positive association between genetically predicted LDL-C and individual, paternal, maternal, and family history of AD, suggesting that high LDL-C level may increase the risks of both individual and familial AD. Lowering LDL-C level to a reasonable range may help reduce the related risk.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Drew R. Seeger, Svetlana A. Golovko, Mikhail Y. Golovko
Article
Cell Biology
Chuan-Min Zhou, Li-Mei Luo, Ping Lin, Qinqin Pu, Biao Wang, Shugang Qin, Qun Wu, Xue-Jie Yu, Min Wu
Summary: This study found that AnxA2 up-regulates the IRE1-XBP1 pathway through p38 MAPK signaling in macrophages infected with P. aeruginosa. XBP1 acts as a positive regulator of innate immunity, enhances autophagy and bacterial clearance, and facilitates NF-kappa B activation to release proinflammatory cytokines mainly in macrophages. These findings identify AnxA2 as a regulator for the XBP1-mediated UPR pathway.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Drew R. Seeger, Svetlana A. Golovko, Bryon D. Grove, Mikhail Y. Golovko
Summary: The study found that the role of cyclooxygenase (COX) in brain angioplasticity is important and may involve mechanisms independent of angiogenic factors. In addition, COX inhibition under chronic hypoxia conditions may increase mortality rate.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Harpreet Kaur, Drew Seeger, Svetlana Golovko, Mikhail Golovko, Colin Kelly Combs
Summary: Alzheimer's disease is a neurodegenerative disease characterized by progressive cognitive impairment, with studies suggesting the involvement of liver cholesterol and bile acid metabolism in its pathophysiology. Experimental results from two different AD mouse lines indicate fundamental deficiencies in liver cholesterol metabolism and bile acid synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
K. S. Campbell, P. G. Keller, L. M. Heinzel, S. A. Golovko, D. R. Seeger, M. Y. Golovko, J. L. Kerby
Summary: The study aimed to investigate whether imidacloprid could cross the blood-brain barrier in adult Northern Leopard frogs exposed to different concentrations, with results showing significantly higher concentrations in the brain of exposed groups compared to the control. Additionally, a dose-response relationship was observed with breakdown products and imidacloprid brain concentrations, indicating that imidacloprid can bioaccumulate in amphibian brains. Behaviorally, exposure to imidacloprid resulted in slower reaction times to food stimuli, with a positive correlation between response time and imidacloprid brain concentration.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Virology
Kai Guo, Dan Justin Kalenda Yombo, Taylor Schmit, Zhihan Wang, Zahrasadat Navaeiseddighi, Venkatachelem Sathish, Ramkumar Mathur, Min Wu, Bony De Kumar, Junguk Hur, Nadeem Khan
Summary: An exuberant host response contributes to influenza A virus (IAV)-mediated lung injury. In this study, the cellular framework and molecular interactions that dictate the development of acute injury in IAV-infected lungs were examined using unbiased single-cell RNA sequencing analysis. The findings revealed the overwhelming recruitment of monocytes and the cell differentiation trajectory to monocyte-derived macrophages, as well as the loss of nonhematopoietic cells during IAV infection. The study also identified the cell-cell communication dynamics and molecular pathways regulating the host responses during IAV-induced lung injury.
JOURNAL OF VIROLOGY
(2022)
Article
Engineering, Environmental
Kaitlyn S. Campbell, Peyton Keller, Svetlana A. Golovko, Drew Seeger, Mikhail Y. Golovko, Jacob L. Kerby
Summary: Neonicotinoids, commonly used neurotoxic insecticides, can enter wetlands through subsurface tile drains and harm nontarget organisms like amphibians. In this study, researchers investigated the impact of imidacloprid, a neonicotinoid, at low concentrations in field-based wetland areas. Results showed that imidacloprid concentrations were significantly higher in the brains and water samples of tile wetland amphibians compared to reference wetlands. The study also found a negative relationship between imidacloprid brain concentration and cerebellum length. These findings suggest that imidacloprid can cross the amphibian blood-brain barrier in natural conditions and affect brain dimensions.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2023)
Article
Parasitology
Brett A. McGregor, Elham Razmjou, Hossein Hooshyar, Drew R. Seeger, Svetlana A. Golovko, Mikhail Y. Golovko, Steven M. Singer, Junguk Hur, Shahram Solaymani-Mohammadi
Summary: This study shows a correlation between the diversity of the fecal microbiome and the development of clinical symptoms during human giardiasis. It is found that individuals with asymptomatic and symptomatic giardiasis have distinctive microbial diversity profiles compared to healthy volunteers.
PARASITES & VECTORS
(2023)
Review
Biochemistry & Molecular Biology
Shugang Qin, Wen Xiao, Chuanmin Zhou, Qinqin Pu, Xin Deng, Lefu Lan, Haihua Liang, Xiangrong Song, Min Wu
Summary: This article comprehensively reviews the biophysical traits, behaviors, virulence factors, invasive regulators, and host defense patterns of P. aeruginosa, providing new directions for future research and contributing to the design of novel and/or alternative therapeutics to combat this clinically significant pathogen.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Review
Biochemistry & Molecular Biology
Shugang Qin, Xiaoshan Tang, Yuting Chen, Kepan Chen, Na Fan, Wen Xiao, Qian Zheng, Guohong Li, Yuqing Teng, Min Wu, Xiangrong Song
Summary: The therapeutic use of mRNA has shown great potential in combating incurable diseases. Recent advances in biotechnology and molecular medicine have allowed for the production of functional proteins/peptides in the human body through mRNA vaccines or therapeutic agents. mRNA vaccines offer the quickest response to large-scale infectious disease outbreaks, such as the current COVID-19 pandemic. Scientists have been working on improving the stability, immunogenicity, translation efficiency, and delivery system of mRNA to achieve efficient and safe delivery. This review comprehensively describes mRNA-based therapeutics, their principles, manufacturing, application, effects, and limitations.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Biochemistry & Molecular Biology
Qinqin Pu, Kai Guo, Ping Lin, Zhihan Wang, Shugang Qin, Pan Gao, Colin Combs, Nadeem Khan, Zhenwei Xia, Min Wu
Summary: TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection, contributing to host defense against the bacterium.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Yue Yuan, Hu Liao, Qiang Pu, Xixian Ke, Xueting Hu, Yongfang Ma, Xinmei Luo, Qianqian Jiang, Yi Gong, Min Wu, Lunxu Liu, Wen Zhu
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)
Letter
Biochemistry & Molecular Biology
Venkataramana K. Sidhaye, Min Wu, Yohannes Tesfaigzi
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Tie Yan, Zheng Heng, He Zhiyao, Yang Jingyun, Shao Bin, Liu Li, Luo Min, Yuan Xia, Liu Yu, Zhang Xiangxian, Li Hongyi, Wu Min, Wei Xiawei
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)
Review
Biochemistry & Molecular Biology
Hongyi Li, Yang Yang, Weiqi Hong, Mengyuan Huang, Min Wu, Xia Zhao
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2020)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)