摘要
阿尔茨海默病 (AD) 是一种慢性神经退行性疾病,是导致认知功能障碍的最常见形式的痴呆症,包括记忆、思维和行为改变,最终导致死亡。 GSK-3(一种来自脯氨酸/丝氨酸 Ki NS 家族的酶)的过度活化与 tau 蛋白的过度磷酸化有关。已知高度磷酸化的 tau 蛋白自组装形成直丝和螺旋丝的缠结与 AD 相关。因此,GSK-3 被认为是发现治疗 AD 新药的潜在靶点。 GSK-3 抑制剂的开发研究受到了广大科学界的极大关注,因为它们针对 AD 和其他疾病,包括 2 型糖尿病、癌症、中风、帕金森病和双相情感障碍。已经设计了多种合成和天然来源的药物来抑制 GSK-3 的活性。然而,需要开发可以选择性抑制 GSK-3 的新型候选药物。因此,本综述总结了 GSK-3 抑制剂在 AD 治疗中的潜力,并讨论了当前药物分子的构效关系以及与之相关的潜在问题。
关键词: 阿尔茨海默病、GSK-3、GSK-3 抑制剂、Tau、β-淀粉样蛋白、神经退行性疾病、蛋白激酶。
Current Drug Targets
Title:GSK-3 Inhibitors: A New Class of Drugs for Alzheimer’s Disease Treatment
Volume: 22 Issue: 15
关键词: 阿尔茨海默病、GSK-3、GSK-3 抑制剂、Tau、β-淀粉样蛋白、神经退行性疾病、蛋白激酶。
摘要: Alzheimer’s disease (AD), a chronic neurodegenerative disease, is the most common form of dementia that causes cognitive function impairment, including memory, thinking, and behavioral changes that ultimately lead to death. The overactivation of GSK-3, an enzyme from the proline/serine Ki NS family, has been associated with hyper-phosphorylation of tau proteins. The self- -assembly of hyper-phosphorylated tau proteins to form tangles of straight and helical filaments is known to be involved in AD. Therefore, GSK-3 has been considered a potential target of novel drug discovery for AD treatment. Research on the development of GSK-3 inhibitors has received enormous attention from the vast scientific community because they are targeted for AD and other diseases, including type 2 diabetes, cancers, stroke, Parkinson’s disease and bipolar disorder. Various drugs of both synthetic and natural origins have been designed to inhibit GSK-3 activity. However, there is a need to develop novel drug candidates that can selectively inhibit GSK-3. Hence, this review summarizes the potential of GSK-3 inhibitors for AD therapy and discusses the structure- activity relationship of current drug molecules and the potential problems associated with them.
Export Options
About this article
Cite this article as:
GSK-3 Inhibitors: A New Class of Drugs for Alzheimer’s Disease Treatment, Current Drug Targets 2021; 22 (15) . https://dx.doi.org/10.2174/1389450122666210114095307
DOI https://dx.doi.org/10.2174/1389450122666210114095307 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
Drug-Targeted Approach with Polymer Nanocomposites for Improved Therapeutics
Polymer nanocomposites have been recognized as an advanced and cutting-edge technique in drug targeting administration. These materials combine the unique features of nanoparticles with the adaptability of polymers to produce highly personalized drug administration devices. Integrating nanoparticles containing pharmaceuticals into a polymer matrix enables researchers to regulate the rates at ...read more
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
Therapeutic Chemical and RNA Design with Artificial Intelligence
Computer-Aided Drug Design (CADD) has emerged as a fundamental component of modern drug discovery. Molecular docking facilitates virtual screening on a large scale through structural simulations. However, traditional CADD approaches face significant limitations, as they can only screen known compounds from existing libraries. PubChem, as the most widely used chemical ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Medical Treatment for Neurocysticercosis: Drugs, Indications and Perspectives
Current Topics in Medicinal Chemistry Antiepileptogenic Effect of Retinoic Acid
Current Neuropharmacology Dorsal Stream Dysfunction in Children. A Review and an Approach to Diagnosis and Management
Current Pediatric Reviews Five Decades of Cuprizone, an Updated Model to Replicate Demyelinating Diseases
Current Neuropharmacology Neurocysticercosis: The Enigmatic Disease
Central Nervous System Agents in Medicinal Chemistry Template Dependent Human DNA Polymerases
Current Topics in Medicinal Chemistry Neurotuberculosis: An Overview
Central Nervous System Agents in Medicinal Chemistry Recent Development in Neuronal Migration Disorders: Clinical, Neuroradiologic and Genetics Aspects
Current Pediatric Reviews Impact of Tracer Retention Levels on Visual Analysis of Cerebral [<sup>18</sup>F]- Florbetaben Pet Images
Current Radiopharmaceuticals The Consumption of Folic Acid During Preconception Period and its Related Knowledge among Iranian Women
Current Women`s Health Reviews Delayed Cerebral Ischemia after Subarachnoid Hemorrhage: From Vascular Spasm to Cortical Spreading Depolarizations
Current Neurovascular Research Influence of Lithium Treatment on GDNF Serum and CSF Concentrations in Patients with Early Alzheimers Disease
Current Alzheimer Research Cerebrospinal Fluid, Brain Electrolytes Balance, and the Unsuspected Intrinsic Property of Melanin to Dissociate the Water Molecule
CNS & Neurological Disorders - Drug Targets Perinatal Management of Pregnancies with Fetal Congenital Anomalies: A Guide to Obstetricians and Pediatricians
Current Pediatric Reviews Quality and Safety in Pediatric Complex Care
Current Pediatric Reviews The Production of Solid Dosage Forms from Non-Degradable Polymers
Current Pharmaceutical Design Muscular Dystrophies: Histology, Immunohistochemistry, Molecular Genetics and Management
Current Pharmaceutical Design Advances in Adjuvant Therapy Against Acute Bacterial Meningitis
Current Drug Targets - Infectious Disorders Vascular Endothelial Primary Cilia: Mechanosensation and Hypertension
Current Hypertension Reviews Dysregulation of Neurotrophic and Haematopoietic Growth Factors in Alzheimer’s Disease: From Pathophysiology to Novel Treatment Strategies
Current Alzheimer Research