The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth

Regulation of adult β-cell mass in pancreatic islets is essential to preserve sufficient insulin secretion in order to appropriately regulate glucose homeostasis. In many tissues mitogens influence development by stimulating D-type cyclins (D1, D2, or D3) and activating cyclin-dependent kinases (CDK4 or CDK6), which results in progression through the G(1) phase of the cell cycle. Here we show that cyclins D2 and D1 are essential for normal postnatal islet growth. In adult murine islets basal cyclin D2 mRNA expression was easily detected, while cyclin D1 was expressed at lower levels and cyclin D3 was nearly undetectable. Prenatal islet development occurred normally in cyclin D2(−)(/)(−) or cyclin D1(+/)(−) D2(−)(/)(−) mice. However, β-cell proliferation, adult mass, and glucose tolerance were decreased in adult cyclin D2(−)(/)(−) mice, causing glucose intolerance that progressed to diabetes by 12 months of age. Although cyclin D1(+/)(−) mice never developed diabetes, life-threatening diabetes developed in 3-month-old cyclin D1(−)(/+) D2(−)(/)(−) mice as β-cell mass decreased after birth. Thus, cyclins D2 and D1 were essential for β-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in β cells could prevent or cure diabetes