Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58201, USA.
CNS Neurol Disord Drug Targets. 2010 Mar;9(1):94-104. doi: 10.2174/187152710790966650.
Calcium is an essential intracellular messenger and serves critical cellular functions in both excitable and non-excitable cells. Most of the physiological functions in these cells are uniquely regulated by changes in cytosolic Ca2+ levels (Ca2+), which are achieved via various mechanisms. One of these mechanism(s) is activated by the release of Ca2+ from the endoplasmic reticulum (ER), followed by Ca2+ influx across the plasma membrane (PM). Activation of PM Ca2+ channel is essential for not only refilling of the ER Ca2+ stores, but is also critical for maintaining Ca2+ that regulates biological functions, such as neurosecretion, sensation, long term potentiation, synaptic plasticity, gene regulation, as well as cellular growth and differentiation. Alterations in Ca2+ homeostasis have been suggested in the onset/progression of neurological diseases, such as Parkinson's, Alzheimer's, bipolar disorder, and Huntington's. Available data on transient receptor potential conical (TRPC) protein indicate that these proteins initiate Ca2+ entry pathways and are essential in maintaining cytosolic, ER, and mitochondrial Ca2+ levels. A number of biological functions have been assigned to these TRPC proteins. Silencing of TRPC1 and TRPC3 has been shown to inhibit neuronal proliferation and loss of TRPC1 is implicated in neurodegeneration. Thus, TRPC channels not only contribute towards normal physiological processes, but are also implicated in several human pathological conditions. Overall, it is suggested that these channels could be used as potential therapeutic targets for many of these neurological diseases. Thus, in this review we have focused on the functional implication of TRPC channels in neuronal cells along with the elucidation of their role in neurodegeneration.
钙是一种必需的细胞内信使，在兴奋和非兴奋细胞中都具有关键的细胞功能。这些细胞中的大多数生理功能都是通过细胞溶质 Ca2+水平（[Ca2+]（i））的变化来独特调节的，这是通过各种机制实现的。其中一种机制是通过内质网（ER）释放 Ca2+激活，随后 Ca2+通过质膜（PM）内流。PM Ca2+通道的激活不仅对于 ER Ca2+库的再填充是必需的，而且对于维持调节生物功能（如神经分泌、感觉、长时程增强、突触可塑性、基因调节以及细胞生长和分化）的 [Ca2+]（i）也是至关重要的。钙稳态的改变已被认为是神经退行性疾病（如帕金森病、阿尔茨海默病、双相情感障碍和亨廷顿病）的发病/进展的原因。关于瞬时受体电位锥形（TRPC）蛋白的现有数据表明，这些蛋白启动 Ca2+进入途径，对于维持细胞溶质、ER 和线粒体 Ca2+水平是必需的。许多生物学功能已被分配给这些 TRPC 蛋白。沉默 TRPC1 和 TRPC3 已被证明可抑制神经元增殖，而 TRPC1 的缺失与神经退行性变有关。因此，TRPC 通道不仅有助于正常的生理过程，而且还与几种人类病理状况有关。总体而言，这些通道可能被用作许多神经退行性疾病的潜在治疗靶点。因此，在本综述中，我们重点关注了 TRPC 通道在神经元细胞中的功能意义，以及它们在神经退行性变中的作用。
