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Abdul HM, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, Patel ES, Baig I, Murphy MP, Levine H, Kraner SD, Norris CM. Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling. J Neurosci. 2009 Oct 14;29(41):12957-69. PubMed.
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University of Kentucky College of Medicine
The connection between DSCR1 and calcineurin/NFAT signaling with AD is indeed interesting. It’s clear that NFATs help increase DSCR1 expression in several different cell types (e.g., 1,2). Elevated DSCR1 levels in AD tissue are therefore consistent with recent reports showing increased calcineurin/NFAT activation during AD (3,4). It’s also clear that DSCR1 interacts directly with calcineurin, but DSCR1 is not a simple calcineurin inhibitor. In fact, DSCR1 can exert permissive effects on calcineurin activity depending on the presence and activation levels of other accessory proteins (5). DSCR1 may, therefore, help attenuate or drive calcineurin/NFAT signaling within AD through negative or positive feedback loops.
References:
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Canellada A, Ramirez BG, Minami T, Redondo JM, Cano E. Calcium/calcineurin signaling in primary cortical astrocyte cultures: Rcan1-4 and cyclooxygenase-2 as NFAT target genes. Glia. 2008 May;56(7):709-22. PubMed.
Abdul HM, Sama MA, Furman JL, Mathis DM, Beckett TL, Weidner AM, Patel ES, Baig I, Murphy MP, Levine H, Kraner SD, Norris CM. Cognitive decline in Alzheimer's disease is associated with selective changes in calcineurin/NFAT signaling. J Neurosci. 2009 Oct 14;29(41):12957-69. PubMed.
Wu HY, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z, Spires-Jones T, Xie H, Arbel-Ornath M, Grosskreutz CL, Bacskai BJ, Hyman BT. Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J Neurosci. 2010 Feb 17;30(7):2636-49. PubMed.
Liu Q, Busby JC, Molkentin JD. Interaction between TAK1-TAB1-TAB2 and RCAN1-calcineurin defines a signalling nodal control point. Nat Cell Biol. 2009 Feb;11(2):154-61. PubMed.
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