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首页> 外文期刊>Clinical and experimental pharmacology & physiology >The neuronal and endocrine roles of RCAN RCAN 1 in health and disease
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The neuronal and endocrine roles of RCAN RCAN 1 in health and disease

机译：RCAN RCAN 1在健康和疾病中的神经元和内分泌作用

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Summary The regulator of calcineurin 1 ( RCAN 1) was first discovered as a gene located on human chromosome 21, expressed in neurons and overexpressed in the brains of Down syndrome individuals. Increased expression of RCAN 1 has been linked with not only Down syndrome‐associated pathology but also an associated neurological disorder, Alzheimer's Disease, in which neuronal RCAN 1 expression is also increased. RCAN 1 has additionally been demonstrated to affect other cell types including endocrine cells, with links to the pathogenesis of β‐cell dysfunction in type 2 diabetes. The primary functions of RCAN 1 relate to the inhibition of the phosphatase calcineurin, and to the regulation of mitochondrial function. Various forms of cellular stress such as reactive oxygen species and hyperglycaemia cause transient increases in RCAN 1 expression. The short term (hours to days) induction of RCAN 1 expression is generally thought to have a protective effect by regulating the expression of pro‐survival genes in multiple cell types, many of which are mediated via the calcineurin/ NFAT transcriptional pathway. However, strong evidence also supports the notion that chronic (weeks‐years) overexpression of RCAN 1 has a detrimental effect on cells and that this may drive pathophysiological changes in neurons and endocrine cells linked to Down syndrome, Alzheimer's Disease and type 2 diabetes. Here we review the evidence related to these roles of RCAN 1 in neurons and endocrine cells and their relationship to these human health disorders.
机译：发明内容首先将钙素素1（RCAN 1）的调节剂作为位于人染色体21上的基因，在神经元中表达并在唐氏综合征个体的大脑中过表达。 RCAN 1的表达增加与不仅与唐氏综合征相关病理学，而且有关的神经疾病，阿尔茨海默病，其中神经元RCAN 1表达也增加。还证明了RCAN 1，以影响包括内分泌细胞的其他细胞类型，与2型糖尿病中β细胞功能障碍的发病机制的联系。 RCAN 1的主要功能涉及磷酸酶钙素的抑制，以及线粒体功能的调节。各种形式的细胞应激，例如反应性氧物质和高血糖导致RCAN 1表达中的瞬时增加。短期（小时到几天）RCAN 1表达的诱导通常认为通过调节多种细胞类型中的促生物质基因的表达具有保护作用，其中许多通过钙素/ NFAT转录途径介导。然而，有力的证据还支持慢性（周年）RCAN 1对细胞的过表达的观念，并且这可能导致与唐氏综合征，阿尔茨海默病和2型糖尿病有关的神经元和内分泌细胞的病理生理变化。在这里，我们审查了与rcan 1在神经元和内分泌细胞中的这些作用相关的证据及其与这些人类健康障碍的关系。

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