Article
Biochemistry & Molecular Biology
Chen Chen, Jian-Wen Liu, Ling-Li Guo, Feng Xiong, Xiao-Qian Ran, Ya-Rong Guo, Yong-Gang Yao, Xiao-Jiang Hao, Rong-Can Luo, Yu Zhang
Summary: Three novel monoterpenoid indole alkaloid dimers (kopoffines A-C) and nine known alkaloids were isolated and identified from the fruits of Kopsia arborea Blume. Kopoffines A-C exhibited significant inhibition against cyclin-dependent kinase 5 and reduced the levels of phosphorylated Tau, which are involved in the formation of neurofibrillary tangles. These findings may have implications for the development of therapeutics for related diseases.
Article
Neurosciences
Benjamin Combs, Kyle R. Christensen, Collin Richards, Andrew Kneynsberg, Rebecca L. Mueller, Sarah L. Morris, Gerardo A. Morfini, Scott T. Brady, Nicholas M. Kanaan
Summary: The study demonstrates that FTLD mutant tau proteins, P301L and R5L, can elicit a toxic effect on axonal transport as monomeric proteins. This suggests a mechanism of tau toxicity involving aberrant activation of a specific PP1 gamma-dependent pathway that disrupts axonal transport in neurons.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Shivani Batra, Shagufta Jahan, Anam Ashraf, Bandar Alharby, Talha Jawaid, Asimul Islam, Imtaiyaz Hassan
Summary: Cyclin-dependent kinase 5 (CDK5) is a serine/threonine-directed kinase primarily found in the brain that plays a crucial role in the development of the central nervous system. Recent research has shown that CDK5 is activated by specific cyclins, which regulate its expression and activity. This review examines the role of CDK5 in neurons, synaptic plasticity, DNA damage repair, and the cell cycle, highlighting its therapeutic potential as a target for neurodegenerative diseases. The structural features of CDK5 and its binding with designed inhibitors are also discussed, providing insights for the development of attractive strategies in therapeutic targeting.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Neurosciences
Li Lin, Xiaodong Liu, Xuejun Cheng, Yujing Li, Marla Gearing, Allan Levey, Xiaoli Huang, Ying Li, Peng Jin, Xuekun Li
Summary: In this study, the altered expression and misregulation of miR-650 in Alzheimer's disease (AD) brains were observed. Bioinformatic analysis predicted that miR-650 targets three AD-associated genes, and experimental confirmation showed that miR-650 significantly reduces their expression levels in vitro. Overexpression of miR-650 was shown to alter CDK5 levels and ameliorate AD pathologies in transgenic mice. These findings suggest that miR-650 influences AD pathogenesis through regulation of CDK5.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Cell Biology
Diksha Kumari, Krishanu Ray
Summary: Phosphorylation of Kinesin subunits and adaptors plays a crucial role in regulating the activity and interactions of Kinesin motors, influencing intracellular transport dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Physical
Ali Akbar Ashkarran, Atiyeh Hosseini, Reza Loloee, George Perry, Ki-Bum Lee, Mikael Lund, Mohammad Reza Ejtehadi, Morteza Mahmoudi
Summary: We investigated the charge transport characteristics of self-assembled monolayers (SAMs) of short tau peptides using electron tunneling rates and quantum mechanical simulation. Our findings showed that the conformation and phosphorylation of short peptides can significantly affect their electron tunneling current and energy levels.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Ilona Faustova, Kaidi Moll, Ervin Valk, Mart Loog, Mihkel Ord
Summary: Cyclins not only activate CDK complexes, but also serve as docking scaffolds for CDK substrates and inhibitors. G1-cyclins in yeast play a specific role in promoting bud growth and polarization, essential for cell survival. The discovery of a specific docking motif in G1-cyclins expands our understanding of cyclin specificity mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Paige Grant, Jitendra Kumar, Satyabrata Kar, Michael Overduin
Summary: The study investigated the effects of two specific kinase inhibitors for CaMK1D on A beta-mediated toxicity in mouse primary cortical neurons. While these inhibitors were able to prevent A beta-induced tau hyperphosphorylation, they were not able to protect cells from A beta induced toxicity. Further research and development may lead to the potential use of these inhibitors as part of a multi-drug strategy to combat Alzheimer's disease.
Article
Biochemistry & Molecular Biology
Jangampalli Adi Pradeepkiran, Manne Munikumar, Arubala P. Reddy, P. Hemachandra Reddy
Summary: The study aimed to understand the protective effects of small molecule ligands for phosphorylated tau in AD progression. Small molecule ligands binding to phosphorylated tau can reduce tau hyperphosphorylation levels in AD and promote mitochondrial biogenesis and synaptic activities while decreasing mitochondrial fission.
HUMAN MOLECULAR GENETICS
(2022)
Article
Cell Biology
Rafael Rivas-Santisteban, Iu Raich, David Aguinaga, Carlos A. Saura, Rafael Franco, Gemma Navarro
Summary: The study discovered a direct interaction between PrPC and NMDAR, which alters the functionality of the receptor. Significant overexpression of NMDAR-PrPC complexes was observed in the AD model, and PrPC exacerbates the axonal transport of Tau and pTau proteins.
Article
Neurosciences
J. Daniel Fenn, Yinyun Li, Jean-Pierre Julien, Peter Jung, Anthony Brown
Summary: Studies have shown that neurofilaments in cultured neurons move rapidly along microtubule tracks. However, the extent of this movement in vivo has been debated. This study found that the majority of neurofilaments in adult peripheral nerves are highly mobile, supporting a dynamic view of the neuronal cytoskeleton.
Article
Neurosciences
Sarah L. Morris, Ming-Ying Tsai, Sarah Aloe, Karin Bechberger, Svenja Konig, Gerardo Morfini, Scott T. Brady
Summary: Research shows that Tau protein is phosphorylated at multiple sites, with some associated with tau pathology. The AT8 antibody can detect a complex phosphoepitope site that significantly increases in Alzheimer's disease and other tauopathies. Phosphorylation events may impact tau conformation, promoting activation of different signaling pathways, which in turn affect axonal transport.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Anusruti Sabui, Mitali Biswas, Pramod Rajaram Somvanshi, Preethi Kandagiri, Madhavi Gorla, Fareed Mohammed, Prasad Tammineni
Summary: Mitochondrial transport and distribution are altered in tauopathy neurons, with reduced anterograde transport and unchanged retrograde transport. The decrease in kinesin-mediated transport and the increase in dynein activity might contribute to the reduced axonal mitochondria in tauopathy neurons, thereby contributing to synaptic deficits in Alzheimer's disease and other tauopathies.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Fernando Gonzalez-Ortiz, Michael Turton, Przemyslaw R. Kac, Denis Smirnov, Enrico Premi, Roberta Ghidoni, Luisa Benussi, Valentina Cantoni, Claudia Saraceno, Jasmine Rivolta, Nicholas J. Ashton, Barbara Borroni, Douglas Galasko, Peter Harrison, Henrik Zetterberg, Kaj Blennow, Thomas K. Karikari
Summary: Blood-based biomarkers for amyloid beta and phosphorylated tau show good diagnostic accuracies and agreements with their corresponding CSF and neuroimaging biomarkers, while the blood-based neurodegeneration marker neurofilament light is not specific to Alzheimer's disease. A newly developed blood-based assay for brain-derived tau has shown equivalent diagnostic performance as CSF total-tau, accurately distinguishing Alzheimer's disease from other neurodegenerative diseases.
Article
Pharmacology & Pharmacy
Dina Medina-Vera, Juan Antonio Navarro, Patricia Rivera, Cristina Rosell-Valle, Alfonso Gutierrez-Adan, Carlos Sanjuan, Antonio Jesus Lopez-Gambero, Ruben Tovar, Juan Suarez, Francisco Javier Pavon, Elena Baixeras, Juan Decara, Fernando Rodriguez de Fonseca
Summary: This study found that d-pinitol inositol can lower tau protein phosphorylation levels by regulating CDK5 activity. This suggests that d-pinitol could be a potential drug for treating neurological disorders such as tauopathies.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.