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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular drug target NantongJiangsu ProvinceChina department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

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Animal models of melanoma: a somatic cell gene delivery mouse model allows rapid evaluation of genes implicated in human melanoma

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Chinese Journal of Cancer 2011年第3期30卷 153-162页

作者： Andrea J. McKinney Sheri L. Holmen department of drug and target discovery Nevada Cancer Institute

The increasing incidence and mortality associated with advanced stages of melanoma are cause for concern. Few treatment options are available for advanced melanoma and the 5-year survival rate is less than 15%. targeted therapies may revolutionize melanoma treatment by providing less toxic and more effective strategies. However, maximizing effectiveness requires further understanding of the molecular alterations that drive tumor formation, progression, and maintenance, as well as elucidating the mechanisms of resistance. Several different genetic alterations identified in human melanoma have been recapitulated in mice. This review outlines recent progress made in the development of mouse models of melanoma and summarizes what these findings reveal about the human disease. We begin with a discussion of traditional models and conclude with the recently developed RCAS/TVA somatic cell gene delivery mouse model of melanoma.

关键词：黑色素瘤小鼠模型基因传递人类疾病体细胞快速评估动物模型治疗方案

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Spinal cord injury regenerative therapy development:integration of design of experiments

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Neural Regeneration Research 2025年第9期20卷 2571-2573页

作者： Yuji Okano Hideyuki Okano Yoshitaka Kase Division of CNS Regeneration and drug discovery International Center for Brain Science(ICBS)Fujita Health UniversityKutsukake-ChoToyoake-ShiAichiJapan department of Extended Intelligence for Medicine The Ishii-Ishibashi LaboratoryKeio University School of MedicineShinanomachiShinjuku-KuTokyoJapan Keio University Regenerative Medicine Research Center Kawasaki-kuKawasaki-shiJapan

Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of *** continue to explo re new stem cell strategies for the treatment of paralysis by transpla nting human induced pluripotent stem cell-derived neural ste m/progenitor cells(hiPSCNS/PCs)into spinal cord injured tissues.

关键词： Spinal paralysis injury

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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and drug discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

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Breaking new ground in photocatalysis: lutetium texaphyrin as a trigger for pyroptosis through biomolecular photoredox reactions

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Science China Chemistry 2025年第1期 1-2页

作者： Qihang Ding Mengrong He Meijia Gu department of Chemistry Korea University department of Ultrasound Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Combinatorial Biosynthesis and drug discovery (MOE) School of Pharmaceutical Sciences Wuhan University

Malignant neoplasms consistently pose a significant threat to global public health [1,2]. In recent years, immunotherapy has demonstrated remarkable clinical success; however, its efficacy is limited by the scarcity of immune cell infiltration within tumor microenvironments. Cell pyroptosis, a gasdermin-mediated process characterized by cellular swelling,rupture, and the release of intracellular contents such as IL-1β, IL-18, ATP, HMGB1, plays a crucial role in this context[3,4].

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Chemo-selective control of Ritter-type reaction by coordinatively unsaturated inorganic salt hydrates

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Organic Chemistry Frontiers 2022年第6期9卷 1541-1549页

作者： Huifang Lai Jiexin Xu Jin Lin Biling Su Daijun Zha department of Medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhou 350004Fujian ProvinceChina Fujian Key Laboratory of drug target discovery and Structural and Functional Research Fujian Medical UniversityChina

The Ritter-type reaction, without relying on a pre-installed functional group, is a highly efficient tool forthe construction of amides. However, the intrinsic chemo-selectivity that determines the generation ofamides or byproducts limits the efficiency and yield of the reaction. From 68 different types of hydrates,we found that a coordinatively unsaturated inorganic salt hydrate, MgSO_(4)·2H_(2)O, controlled chemoselectivity and eliminated the shortcomings of other synthesis approaches. To rationalize the differencesin selectivity of inorganic salt hydrates, we analyzed their corresponding water content, alkalinity, anions,and cations. MgSO_(4)·2H_(2)O was used with diverse scaffolds and C–H oxygenations, which demonstratedits generality in synthetic utility. Because it is readily available and it significantly improves yield, we expectthat MgSO_(4)·2H_(2)O will have broad application for Ritter-type reactions.

关键词： inorganic hydrate unsaturated

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Analysis of receptor-ligand binding by photoaffinity cross-linking

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Science China Chemistry 2014年第2期57卷 232-242页

作者： XU Bin WU Ling department of Biochemistry and Center for drug discovery Virginia TechBlacksburgVA 24061USA

Photoaffinity cross-linking is a fast developing technology for biomolecular interactions,including receptor-ligand *** chemical mechanisms of the most commonly used photoactivatable probes and their respective photochemistry are *** review focuses on the expanding utilities of this technology as a result of recent advances in the(i)identification of receptor contact sites,(ii)monitoring ligand-induced receptor conformational changes,(iii)identification of global binding surfaces,(iv)binding mode analysis using bifunctional photo-probes,(v)application of biosynthetic photo-probes,and(vi)examples of novel target discovery using this *** and future potential of this approach are also discussed.

关键词： photoaffinity cross-linking receptor-ligand interaction photoscanning bifunctional photo-probe biosynthetic photo-probe novel receptor discovery

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Dual PPAR delta/gamma agonist offer therapeutic potential for Alzheimer's disease

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Neural Regeneration Research 2024年第6期19卷 1175-1176页

作者： Ian Steinke Meenakshi Singh Rajesh Amin department of drug discovery and Development Auburn UniversityAuburn AlabamaALUSA

The increasing incidence of Alzheimer's disease(AD)in the aging population,indicates the critical need for the development of novel targeted molecular therapies for ameliorating AD ***,clinical and preclinical evidence demonstrates that peroxisomal proliferator activating receptors(PPAR)agonists regulate energy and lipid homeostasis in models of diabetes,as well as improve spatial memory in animal models of AD(Khan et al.,2019).

关键词： Alzheimer clinical homeostasis

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A Therapeutic Sheep in Metastatic Wolf’s Clothing: Trojan Horse Approach for Cancer Brain Metastases Treatment

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Nano-Micro Letters 2022年第7期14卷 140-156页

作者： Hai-jun Liu Mingming Wang Shanshan Shi Xiangxiang Hu Peisheng Xu department of drug discovery and Biomedical Sciences College of PharmacyUniversity of South CarolinaColumbiaSC 29208USA

Early-stage brain metastasis of breast cancer(BMBC), due to the existence of an intact blood–brain barrier(BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly(D, L-lactic-co-glycolic acid) nanoparticle(DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering the brain of both healthy and early-stage BMBC mouse models. Consequently, DOX-PLGA@CM effectively reaches the metastatic tumor lesions in the brain, slows down cancer progression, reduces tumor burden, and extends the survival time for the BMBC ***, the simplicity and easy scale-up of the design opens a new window for the treatment of BMBC and other brain metastatic cancers.

关键词： Trojan horse Brain metastasis Blood-brain barrier Cell membrane Nanomedicine

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The inhibition of Typhonium flagelliforme Lodd. Blume leaf extract on COX-2 expression of Wi Dr colon cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2016年第3期6卷 251-255页

作者： Agustina Setiawati Handika Immanuel Mery Tri Utami department of drug Design and discovery Faculty of Pharmacy Sanata Dharma University

Objective: To determine the inhibition activity of Typhonium flagelliforme Lodd. Blume(T. flagelliforme) leaf extract on cyclooxygenase 2(COX-2) expression of colon cancer ***: T. flagelliforme leaf extract was prepared to macerate in ethyl acetate. In vitro anticancer activity was assayed by MTT method on Wi Dr colon cancer cells. This study applied apoptosis induction assay to investigate the mechanism of cell death using double staining method. COX-2 expression was stained by ***: T. flagelliforme showed anticancer activity and induced apoptosis on Wi Dr cells through inhibition of COX-2 expression with IC5070 mg/m ***: This study showed that T. flagelliforme is a promising chemopreventive agent for colon cancer through COX-2 inhibition.

关键词： Typhonium flagelliforme Colon cancer WiDr Cyclooxygenase 2

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