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基于神经疾病多方面机制和特点的理想动物模型:现状与挑战

Ideal animal models according to multifaceted mechanisms and peculiarities in neurological disorders: present and challenges.

作者信息

Lamichhane Shrawani, Seo Jo-Eun, Jeong Ji Hoon, Lee Sooyeun, Lee Sangkil

机构信息

College of Pharmacy, Chung-Ang University, 84 Heukseok-Ro, Dongjak-Gu, Seoul, 06974, Republic of Korea.

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, 06974, Republic of Korea.

出版信息

Arch Pharm Res. 2025 Jan;48(1):62-88. doi: 10.1007/s12272-024-01527-9. Epub 2024 Dec 18.

Abstract

Neurological disorders, encompassing conditions such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.

摘要

神经疾病,包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩侧索硬化症(ALS)等病症,构成了一项重大的全球健康挑战,影响着全球数百万人。随着人口老龄化和预期寿命的延长,这些疾病的患病率正在迅速上升,导致每年超过数万亿美元的巨大经济负担。动物模型在理解这些疾病的潜在机制和开发有效治疗方法方面发挥着关键作用。包括啮齿动物、非人灵长类动物和果蝇在内的各种物种被用于复制人类神经疾病的特定方面。然而,选择理想的动物模型需要仔细考虑其与人类疾病状况的接近程度以及模拟疾病病理生物学和药理反应的能力。已经开发了一种动物模型质量评估(AMQA)工具来促进这一选择过程,重点是根据模型与人类状况和疾病病理生物学的相似性来评估模型。因此,将与疾病相关的内在和外在因素纳入研究目标有助于构建一个生物信息矩阵,以比较动物模型和人类疾病之间的疾病进展。最终,选择理想的动物疾病模型取决于其预测效度、表面效度和结构效度,确保转化研究工作的相关性和可靠性。

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