Mooradian Arshag D, Haas Michael J
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Florida Jacksonville College of Medicine, 653-1 West 8th Street, Jacksonville, FL 32209, USA.
Cells. 2025 Jan 18;14(2):140. doi: 10.3390/cells14020140.
Thyroid dysfunction is associated with a number of neuropsychiatric manifestations. Cognitive decline is a common feature of hypothyroidism and clinical or subclinical hyperthyroidism. In addition, there is a significant association between thyroid hormone (TH) levels and the degree of cognitive impairment in Parkinson's disease (PD). The pathophysiology of TH-related neurodegeneration include changes in the blood-brain barrier, increased cellular stress, altered processing of β-amyloid precursor protein and the effect of TH on neuronal cell viability. The neurotoxicity of TH is partially mediated by the thyroid hormone responsive protein (THRP). This protein is 83% homologous to mouse c-Abl-interacting protein-2 (Abi2), a c-Abl-modulating protein with tumor suppressor activity. In cell cultures, increasing THRP expression either with TH treatment or exogenously through transfecting neuronal or PC 12 cells causes cell necrosis. The expression of exogenous THRP in other cells such as the colonic epithelial cell line Caco-2 and the glial cell line U251 has no effect on cell viability. The effect of THRP on cell viability is not modulated by c-Abl tyrosine kinase. The causal relationship between specific biochemical perturbations in cerebral tissue and thyroid dysfunction remains to be elucidated.
甲状腺功能障碍与多种神经精神表现相关。认知功能下降是甲状腺功能减退以及临床或亚临床甲状腺功能亢进的常见特征。此外，甲状腺激素（TH）水平与帕金森病（PD）的认知障碍程度之间存在显著关联。TH相关神经变性的病理生理学包括血脑屏障的变化、细胞应激增加、β-淀粉样前体蛋白加工过程改变以及TH对神经元细胞活力的影响。TH的神经毒性部分由甲状腺激素反应蛋白（THRP）介导。该蛋白与小鼠c-Abl相互作用蛋白-2（Abi2）有83%的同源性，Abi2是一种具有肿瘤抑制活性的c-Abl调节蛋白。在细胞培养中，通过TH处理或通过转染神经元或PC 12细胞外源性增加THRP表达会导致细胞坏死。外源性THRP在其他细胞如结肠上皮细胞系Caco-2和胶质细胞系U251中的表达对细胞活力没有影响。THRP对细胞活力的影响不受c-Abl酪氨酸激酶调节。脑组织中特定生化紊乱与甲状腺功能障碍之间的因果关系仍有待阐明。
