Daimon Caitlin M, Chirdon Patrick, Maudsley Stuart, Martin Bronwen
Metabolism Unit, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Am J Alzheimers Dis (Columbia). 2013;1(1). doi: 10.7726/ajad.2013.1003.
Thyrotropin releasing hormone (TRH) is primarily known as the central regulator of the hypothalamic-pituitary-thyroid (HPT) axis. However, TRH also exerts a variety of central nervous system effects independent from its activity in the HPT axis. With advancing age, decreases in TRH synthesis, expression, and activity have been demonstrated. Associated with this emerging evidence suggests that TRH is implicated in neurodegenerative diseases of aging, including Alzheimer's disease and Parkinson's disease. TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation. In this review, we will provide an overview of some of the roles of TRH, outside of the HPT axis, associated with pathological aging and neurodegeneration and we shall discuss the potential of TRH and TRH analogs for the treatment of neurodegenerative diseases.
促甲状腺激素释放激素（TRH）主要作为下丘脑 - 垂体 - 甲状腺（HPT）轴的中枢调节因子为人所知。然而，TRH也会发挥多种独立于其在HPT轴活性的中枢神经系统效应。随着年龄的增长，已证实TRH的合成、表达和活性会下降。与此新出现的证据相关联的是，TRH与包括阿尔茨海默病和帕金森病在内的衰老神经退行性疾病有关。TRH及其合成类似物已被公认为间脑和脊髓神经元中的营养因子，以及对抗氧化应激、谷氨酸毒性、半胱天冬酶诱导的细胞死亡、DNA片段化和炎症的神经保护剂。在本综述中，我们将概述TRH在HPT轴之外与病理性衰老和神经退行性变相关的一些作用，并讨论TRH和TRH类似物治疗神经退行性疾病的潜力。
