Jie Miao, Yanli Zhang, Chen Su, Qiandan Zheng, Junhong Guo
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引用次数: 0
摘要
阿尔茨海默病(AD)是导致老年人痴呆症的主要原因,由于治疗方案有限,只能延缓认知能力衰退,给公共卫生带来了巨大挑战。老年痴呆症与能量代谢受损和神经营养信号减少有关。胰岛素样生长因子(IGF)信号通路对中枢神经系统(CNS)的发育、代谢、修复、认知和情绪调节至关重要,它包括 IGF-1、IGF-2、IGF-1R、IGF-2R、胰岛素受体(IR)和六种胰岛素样生长因子结合蛋白(IGFBPs)。研究发现,在注意力缺失症患者和注意力缺失症模型中,IGF 信号传导存在异常。IGFs、受体、IGFBPs 的表达失调,以及下游磷脂酰肌醇3-激酶-蛋白激酶B(PI3K/AKT)和丝裂原活化蛋白激酶(MAPK)通路的紊乱,共同增加了注意力缺失症的易感性。研究表明,调节 IGF 通路可改善 AD 病理和认知能力下降。本综述探讨了IGF信号在AD进展过程中的中枢神经系统病理生理学,并评估了靶向IGF系统作为一种新型治疗策略的潜力。进一步的研究对于阐明异常的 IGF 信号传导如何导致 AD 的发展、了解潜在的分子机制以及评估基于 IGF 的治疗方法的安全性和有效性至关重要。
Insulin-Like Growth Factor Signaling in Alzheimer's Disease: Pathophysiology and Therapeutic Strategies.
Alzheimer's disease (AD) is the leading cause of dementia among the elderly population, posing a significant public health challenge due to limited therapeutic options that merely delay cognitive decline. AD is associated with impaired energy metabolism and reduced neurotrophic signaling. The insulin-like growth factor (IGF) signaling pathway, crucial for central nervous system (CNS) development, metabolism, repair, cognition, and emotion regulation, includes IGF-1, IGF-2, IGF-1R, IGF-2R, insulin receptor (IR), and six insulin-like growth factor binding proteins (IGFBPs). Research has identified abnormalities in IGF signaling in individuals with AD and AD models. Dysregulated expression of IGFs, receptors, IGFBPs, and disruptions in downstream phosphoinositide 3-kinase-protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) pathways collectively increase AD susceptibility. Studies suggest modulating the IGF pathway may ameliorate AD pathology and cognitive decline. This review explores the CNS pathophysiology of IGF signaling in AD progression and assesses the potential of targeting the IGF system as a novel therapeutic strategy. Further research is essential to elucidate how aberrant IGF signaling contributes to AD development, understand underlying molecular mechanisms, and evaluate the safety and efficacy of IGF-based treatments.
期刊介绍:
Molecular Neurobiology is an exciting journal for neuroscientists needing to stay in close touch with progress at the forefront of molecular brain research today. It is an especially important periodical for graduate students and "postdocs," specifically designed to synthesize and critically assess research trends for all neuroscientists hoping to stay active at the cutting edge of this dramatically developing area. This journal has proven to be crucial in departmental libraries, serving as essential reading for every committed neuroscientist who is striving to keep abreast of all rapid developments in a forefront field. Most recent significant advances in experimental and clinical neuroscience have been occurring at the molecular level. Until now, there has been no journal devoted to looking closely at this fragmented literature in a critical, coherent fashion. Each submission is thoroughly analyzed by scientists and clinicians internationally renowned for their special competence in the areas treated.