Sun Yuyang, Sukumaran Pramod, Schaar Anne, Singh Brij B
a Department of Basic Science ; School of Medicine and Health Sciences, University of North Dakota ; Grand Forks , ND USA.
Channels (Austin). 2015;9(5):253-61. doi: 10.1080/19336950.2015.1075675. Epub 2015 Jul 28.
Calcium (Ca(2+)) and magnesium (Mg(2+)) ions have been shown to play an important role in regulating various neuronal functions. In the present review we focus on the emerging role of transient potential melastatin-7 (TRPM7) channel in not only regulating Ca(2+) and Mg(2+) homeostasis necessary for biological functions, but also how alterations in TRPM7 function/expression could induce neurodegeneration. Although eight TRPM channels have been identified, the channel properties, mode of activation, and physiological responses of various TRPM channels are quite distinct. Among the known 8 TRPM channels only TRPM6 and TRPM7 channels are highly permeable to both Ca(2+) and Mg(2+); however here we will only focus on TRPM7 as unlike TRPM6, TRPM7 channels are abundantly expressed in neuronal cells. Importantly, the discrepancy in TRPM7 channel function and expression leads to various neuronal diseases such as Alzheimer disease (AD) and Parkinson disease (PD). Further, it is emerging as a key factor in anoxic neuronal death and in other neurodegenerative disorders. Thus, by understanding the precise involvement of the TRPM7 channels in different neurodegenerative diseases and by understanding the factors that regulate TRPM7 channels, we could uncover new strategies in the future that could evolve as new drug therapeutic targets for effective treatment of these neurodegenerative diseases.
钙(Ca(2+))和镁(Mg(2+))离子已被证明在调节各种神经元功能中发挥重要作用。在本综述中,我们重点关注瞬时电位褪黑素7(TRPM7)通道的新作用,它不仅调节生物功能所需的Ca(2+)和Mg(2+)稳态,还涉及TRPM7功能/表达的改变如何诱导神经退行性变。虽然已鉴定出8种TRPM通道,但各种TRPM通道的通道特性、激活模式和生理反应截然不同。在已知的8种TRPM通道中,只有TRPM6和TRPM7通道对Ca(2+)和Mg(2+)都具有高度通透性;然而,在这里我们将只关注TRPM7,因为与TRPM6不同,TRPM7通道在神经元细胞中大量表达。重要的是,TRPM7通道功能和表达的差异会导致各种神经元疾病,如阿尔茨海默病(AD)和帕金森病(PD)。此外,它正在成为缺氧性神经元死亡和其他神经退行性疾病的关键因素。因此,通过了解TRPM7通道在不同神经退行性疾病中的精确作用以及调节TRPM7通道的因素,我们未来可能会发现新的策略,这些策略可能会发展成为有效治疗这些神经退行性疾病的新药物治疗靶点。