Article
Biochemistry & Molecular Biology
Maxim M. M. Zaigraev, Ekaterina N. N. Lyukmanova, Alexander S. S. Paramonov, Zakhar O. O. Shenkarev, Anton O. O. Chugunov
Summary: Ly6/uPAR proteins with GPI-anchors have various positions and orientations on the membrane surface, regardless of the linker length between the LU domain and GPI-anchor. The proteins interact with the membrane through polypeptide parts and glycans. Different proteins have different contact regions with the membrane and unique orientations, indicating that GPI-anchoring does not determine the optimal pre-orientation for receptor interaction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Alexander S. Paramonov, Mikhail A. Shulepko, Alexey M. Makhonin, Maxim L. Bychkov, Dmitrii S. Kulbatskii, Andrey M. Chernikov, Mikhail Yu Myshkin, Sergey Shabelnikov, Zakhar O. Shenkarev, Mikhail P. Kirpichnikov, Ekaterina N. Lyukmanova
Summary: In this study, we identified and analyzed the genomes of starfish A. rubens and A. planci, and predicted several proteins containing three-finger domains. One of these proteins, Lystar5, was expressed in A. rubens and negatively modulated the cholinergic system in hippocampal neurons.
Article
Biochemistry & Molecular Biology
Maxim L. Bychkov, Aizek B. Isaev, Alexander A. Andreev-Andrievskiy, Konstantin Petrov, Alexander S. Paramonov, Mikhail P. Kirpichnikov, Ekaterina N. Lyukmanova
Summary: Alzheimer's disease is a neurodegenerative disease characterized by the accumulation of toxic forms of beta-amyloid and dysfunction of the cholinergic system. This study found decreased expression of Ly6/uPAR proteins targeting nicotinic acetylcholine receptors (nAChRs) in the cerebellum of AD mice, as well as diminished co-localization of the neuromodulator Lynx1 with alpha 7-nAChR and increased co-localization of A beta 1-42 with this receptor. Additionally, the decreased expression of the anti-inflammatory transcription factor KLF4 and increased expression of the inflammatory cytokine TNF-alpha were observed. These findings suggest that the dysregulation of Ly6/uPAR proteins results in cholinergic system dysfunction and neuroinflammation in the cerebellum.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Yan Fu, Hongfei Ci, Wei Du, Qiongzhu Dong, Huliang Jia
Summary: In this study, the role of CHRNA5 in hepatocellular carcinoma (HCC) was investigated. Increased expression of CHRNA5 in HCC tissues was found to be positively correlated with tumor stage and worse survival in patients. Both in vitro and in vivo assays showed that CHRNA5 regulates HCC proliferation through the YAP pathway and promotes stemness through stemness-associated genes. Furthermore, CHRNA5 enhances HCC metastasis by regulating epithelial-mesenchymal transition (EMT)-associated genes. It was also observed that CHRNA5 affects the sensitivity of HCC to sorafenib treatment. These findings indicate that CHRNA5 plays a crucial role in HCC progression and drug resistance.
Article
Multidisciplinary Sciences
Sridevi Venkatesan, Tianhui Chen, Yupeng Liu, Eric E. Turner, Shreejoy J. Tripathy, Evelyn K. Lambe
Summary: The study reveals that Chrna5-expressing neurons play a crucial role in attention and offer potential targets for improvement. By using opto-physiological experiments and single-cell transcriptomics, researchers identify a distinct population of acetylcholine super-responders within Chrna5+ neurons and discover molecular markers that define their identity. Manipulation of the regulation of nicotinic responses in these neurons provides new strategies for the treatment of attention disorders.
Review
Biochemistry & Molecular Biology
Yosuke Kanno
Summary: Fibrotic diseases are characterized by excessive extracellular matrix deposition leading to tissue overgrowth. The progression of fibrosis is driven by increased ECM production and impaired degradation, which can result from inflammation, vascular dysfunction, and immune abnormalities. Recent studies have shown that the urokinase plasminogen activator (uPA) and its receptor (uPAR) play a role in regulating the inflammatory response, vascular homeostasis, and immune homeostasis, making them potential therapeutic targets for fibrotic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Julia K. Brynildsen, Kechun Yang, Crystal Lemchi, John A. Dani, Mariella De Biasi, Julie A. Blendy
Summary: The SNP D398N in the CHRNA5 gene has been associated with nicotine and opiate dependence. By using CRISPR/Cas9 genome editing, mice with the risk-associated allele were generated and it was found that this genotype may enhance opioid reward specifically in females. The response of DA neurons to morphine was altered in Chrna5 A/A mice, and increased opiate reward was observed two weeks after conditioning.
Article
Cell Biology
Karo Talvio, Rimante Minkeviciene, Kayla G. Townsley, Venkat Swaroop Achuta, Laura M. Huckins, Padraic Corcoran, Kristen J. Brennand, Maija L. Castren
Summary: This study compared the transcriptomes of human neural progenitors (NPCs) generated from patient-derived induced pluripotent stem cells (iPSCs) of three fragile X syndrome (FXS) and three control male donors. The results showed altered expression of several genes related to triplet repeat instability, RNA splicing, testes development, and pathways previously shown to be affected in FXS. The study also revealed disturbed growth linked to reduced expression of LYNX1, suggesting dysregulated cholinergic system. The findings highlight the potential of human iPSCs in disease modeling and therapeutic interventions for FXS.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Medicine, General & Internal
Filomena Napolitano, Nunzia Montuori
Summary: The plasminogen activation system plays a crucial role not only in regulating fibrinolysis, but also in various biological processes. The link between this system and angioedema has become a topic of scientific debate, with an increasing number of studies investigating its involvement in recent years.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Kexin Li, Qingji Huo, Kazumasa Minami, Keisuke Tamari, Kazuhiko Ogawa, Sungsoo Na, Melissa L. Fishel, Bai-Yan Li, Hiroki Yokota
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a tough and aggressive cancer with low survival rates. This study explores a unique therapeutic approach by utilizing the tumor-modifying potential of oncogenic markers found in PDAC. Surprisingly, certain proteins that are highly expressed in PDAC and associated with poor survival actually exhibit tumor-suppressing qualities when introduced extracellularly. One such protein, PSCA, known to be harmful to patients, can actually help weaken and inhibit the spread of cancer cells when placed outside of the cells. Additionally, PSCA works synergistically with other chemotherapeutic agents used to treat cancer. This discovery has the potential to revolutionize cancer treatment by utilizing proteins that were previously considered to be part of the problem.
Article
Psychiatry
Erin Meyers, Zachary Werner, David Wichman, Hunter L. Mathews, Richard A. Radcliffe, Joseph H. Nadeau, Jerry A. Stitzel
Summary: The gene CHRNA5 is strongly associated with nicotine intake, with its reduced or lost function leading to increased nicotine consumption. By studying genetic modifiers that affect nicotine intake in Chrna5 knockout mice, researchers identified loci that may influence nicotine consumption independently of the Chrna5 genotype.
FRONTIERS IN PSYCHIATRY
(2021)
Review
Neurosciences
Julia K. Brynildsen, Julie A. Blendy
Summary: Genetics, specifically the SNP D398N in the CHRNA5 gene, has been linked to addiction to various substances including nicotine, opioids, cocaine, and alcohol. Studies in humans, rodents, and cell lines suggest that this SNP broadly influences response to drugs of abuse in a non-substance-specific manner, shedding light on the role of the cholinergic system in reward and addiction vulnerability.
Article
Multidisciplinary Sciences
Zhongshun Liu, Congwei Jiang, Zhangmengxue Lei, Sihan Dong, Linlin Kuang, Chenxu Huang, Ying Gao, Mu Liu, Hui Xiao, Patrick Legembre, Jae U. Jung, Huaping Liang, Xiaozhen Liang
Summary: Type I interferons (IFNs) are the first line of defense against invading pathogens. This study identified a previously unknown protein, PINLYP, that interacts with TBK1 to induce the production of type I IFN. Loss of PINLYP impaired the activation of IRF3 and the production of IFN induced by various viruses and Toll-like receptor ligands. Mice lacking PINLYP were more susceptible to lethal virus infection, highlighting the importance of PINLYP in the host defense against viral infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Julie M. Miwa
Summary: Nicotinic receptors are ligand-gated ion channels responding to acetylcholine and nicotine, playing a role in transducing environmental information in normal and disease states. Targeting the complex of the nicotinic receptor, including lynx1 accessory proteins, may be key to unlocking therapeutic potential.
CURRENT OPINION IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Talulla B. Palumbo, Julie. M. Miwa
Summary: Despite solid data supporting the involvement of nicotinic receptors in neurological and neuropsychiatric diseases, their potential as a therapeutic target has not been fully realized due to complex factors such as the widespread action of the cholinergic system and the biophysical mechanism of nicotinic receptors. Conventional drug development strategies focus on receptor subtype-specific action, while exploring the broad agonist nicotine in the clinic. Prototoxins, a little-explored avenue, show promise as nicotinic receptor drugs and have potential advantages over targeting specific receptor subtypes. Their allosteric effects and binding specificity provide possibilities for more effective and nuanced therapeutic approaches.
PHARMACOLOGICAL RESEARCH
(2023)