Presenilins FormERCa Leak Channels, a Function Disrupted by Familial Alzheimer’s Disease-Linked Mutations
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چکیده
Huiping Tu, Omar Nelson, Arseny Bezprozvanny, Zhengnan Wang, Sheu-Fen Lee, Yi-Heng Hao, Lutgarde Serneels, Bart De Strooper, Gang Yu, and Ilya Bezprozvanny* Department of Physiology Center for Basic Neuroscience UT Southwestern Medical Center at Dallas, Dallas, TX, 75390, USA Neuronal Cell Biology and Gene Transfer, Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB4) and KU Leuven, 3000 Leuven, Belgium *Contact: [email protected] DOI 10.1016/j.cell.2006.06.059
منابع مشابه
Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Mutations in presenilins 1 and 2 (PS1 and PS2) account for approximately 40% of familial AD (FAD) cases. FAD mutations and genetic deletions of presenilins have been associated with calcium (Ca(2+)) signaling abnormalities. We demonstrate that wild-type presenilins, but not PS1-M146V and PS2-N141I FAD mutants...
متن کاملFamilial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1.
Mutations in presenilins are responsible for approximately 40% of all early-onset familial Alzheimer disease (FAD) cases in which a genetic cause has been identified. In addition, a number of mutations in presenilin-1 (PS1) have been suggested to be associated with the occurrence of frontal temporal dementia (FTD). Presenilins are highly conserved transmembrane proteins that support cleavage of...
متن کاملNeurobiology of Disease Role of Presenilins in Neuronal Calcium Homeostasis
Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disorder. Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca 2 ) signaling abnormalities. To explain these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passive Ca 2 leak channels. To directly investigate the role of presenilins in neuronal ER Ca 2 homeo...
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Mutations in the presenilins that cause familial Alzheimer's disease alter the activity of these proteases to increase generation of an aggregation-prone isoform of the amyloid β-peptide (Aβ). How these mutations do so has been unclear. Sannerud et al. now show that regulation of subcellular localization plays a central role, advancing our understanding of the cell biology of Alzheimer's disease.
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Mutations in the presenilin genes cause the majority of early-onset familial Alzheimer’s disease. Recently, presenilin mutations have been identified in patients with dilated cardiomyopathy (DCM), a common cause of heart failure and the most prevalent diagnosis in cardiac transplantation patients. However, the molecular mechanisms, by which presenilin mutations lead to either AD or DCM, are not...
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تاریخ انتشار 2007