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The neuronal and endocrine roles of RCAN 1 in health and disease
Author(s) -
Peiris Heshan,
Keating Damien J.
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12884
Subject(s) - calcineurin , nfat , biology , disease , endocrine system , cell type , endocrinology , pathogenesis , medicine , regulator , gene expression , microbiology and biotechnology , cell , neuroscience , gene , immunology , genetics , hormone , transplantation
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.