Undad de Investigación, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), 11002 Cádiz, Spain.
Área de Genética, Departamento de Biomedicina, Biotecnología y Salud Pública, Universidad de Cádiz, 11002 Cádiz, Spain.
Int J Mol Sci. 2022 May 29;23(11):6089. doi: 10.3390/ijms23116089.
Huntington's disease (HD) is a neurodegenerative disorder caused by a toxic, aggregation-prone expansion of CAG repeats in the HTT gene with an age-dependent progression that leads to behavioral, cognitive and motor symptoms. Principally affecting the frontal cortex and the striatum, mHTT disrupts many cellular functions. In fact, increasing evidence shows that peripheral tissues are affected by neurodegenerative diseases. It establishes an active crosstalk between peripheral tissues and the brain in different neurodegenerative diseases. This review focuses on the current knowledge of peripheral tissue effects in HD animal and cell experimental models and identifies biomarkers and mechanisms involved or affected in the progression of the disease as new therapeutic or early diagnostic options. The particular changes in serum/plasma, blood cells such as lymphocytes, immune blood cells, the pancreas, the heart, the retina, the liver, the kidney and pericytes as a part of the blood-brain barrier are described. It is important to note that several changes in different mouse models of HD present differences between them and between the different ages analyzed. The understanding of the impact of peripheral organ inflammation in HD may open new avenues for the development of novel therapeutic targets.
亨廷顿病(HD)是一种神经退行性疾病,由 HTT 基因中 CAG 重复序列的毒性、易于聚集的扩增引起,其进展具有年龄依赖性,导致行为、认知和运动症状。mHTT 主要影响额叶皮层和纹状体,破坏许多细胞功能。事实上,越来越多的证据表明,周围组织也受到神经退行性疾病的影响。它在不同的神经退行性疾病中建立了外周组织与大脑之间的活跃串扰。本综述重点介绍了 HD 动物和细胞实验模型中外周组织效应的最新知识,并确定了疾病进展中涉及或受影响的生物标志物和机制,作为新的治疗或早期诊断选择。描述了血清/血浆、淋巴细胞等血细胞、免疫血细胞、胰腺、心脏、视网膜、肝脏、肾脏和血脑屏障的一部分周细胞的特殊变化。值得注意的是,HD 不同小鼠模型中的几种变化在它们之间以及分析的不同年龄之间存在差异。了解外周器官炎症对 HD 的影响可能为开发新的治疗靶点开辟新途径。