Presenilin mutations and calcium signaling defects in the nervous and immune systems

Mattson, Mark P.; Chan, Sic L.; Camandola, Simonetta

doi:10.1002/bies.1103

Cited by 59 publications

(29 citation statements)

References 93 publications

(110 reference statements)

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“…Moreover, growing evidence suggests that mutant PS1 and/or mutant APP sensitize cells to apoptosis, by linking perturbed calcium homeostasis to the pathogenic action of AD-specific mutations. Again, these changes are not limited to neurons (Mattson et al, 1993;Parshad et al, 1996;Sulger et al, 1999;Mattson et al, 2001;Eckert et al, 2001b;Eckert et al, 2001c). Interestingly, different mutations in both genes, APP and PS1, appear to have the same final effect of an increased vulnerability to cell death in lymphocytes.…”

Section: Neuromolecular Medicinementioning

confidence: 97%

“…The use of these easily accessible cells from AD patients complements studies of autopsy samples in a meaningful matter and provides a useful tool to investigate dynamic processes such as the regulation of cell death pathways, signal transduction mechanisms, intracellular calcium regulation, and oxidative metabolism (Mecocci et al, 1994;Gibson et al, 1996;Eckert et al, 1998;Gibson et al, 2000;Mattson et al, 2001;Eckert et al, 2001a;Gibson et al, 2002;Mecocci et al, 2002). Abnormalities in each of these processes occur in AD and can be linked to neuronal death and brain dysfunction.…”

Section: Neuromolecular Medicinementioning

confidence: 99%

“…Some of these pathological changes are also related to aging and are additionally altered in AD by common or divergent mechanisms (Quadri et al, 1996;Poulin et al, 1996;Eckert et al, 1997a;Eckert et al, 1997b;Schindowski et al, 2000). Cell culture experiments also suggest that defects in the cellular calcium stores, ability to handle oxidative stress, and to respond to metabolic impairment, link the FADcausing PS1 mutations to the disease process (Mattson et al, 2001). Importantly, our recent findings in lymphocytes from PS1 mutant transgenic mice mirror comparable findings in lymphocytes from AD patients (Parshad et al, 1996;Eckert et al, 1998;Eckert et al, 2001a) indicating that disturbances in the metabolism of ROS inside cells, abnormal calcium homeostasis, and increased susceptibility to cell death may contribute to the pathogenic mechanisms of PS-1 mutations in vivo.…”

Section: Neuromolecular Medicinementioning

confidence: 99%

“…Several recent findings have linked Aβ toxicity (Loo et al, 1993) and increased Aβ production resulting from FAD-related APP or PS1 mutations to cell death Mattson et al, 2001;Selkoe, 2001). Recent findings indicate that the expression of mutant PS1 or mutant APP in PC12 cells sensitizes cells to apoptosis (Guo et al, 1997;Eckert et al, 2001c;Marques et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease

Schindowski

Kratzsch

Peters

et al. 2003

NMM

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The identification of specific genetic and amyloid precursor protein [APP] mutations) and environmental factors responsible for Alzheimer's disease (AD) has revealed evidence for a shared pathway of neuronal death. Moreover, AD-specific cell defects may be observed in many other nonneuronal cells (e.g., lymphocytes). Thus, lymphocytes may serve as a cellular system in which to study risk factors of sporadic, as well as genetic AD in vivo. The aim of our present study was to clarify whether lymphocytes bearing genetic or sporadic risk factors of AD share an increased susceptibility to cell death. Additionally we examined whether a cell typespecific vulnerability pattern was present and how normal aging, the main risk factor of sporadic AD, contributes to changes in susceptibility to cell death. Here, we report that lymphocytes affected by sporadic or genetic APP and PS1 AD risk factors share an increased vulnerability to cell death and exhibit a similar cell type-specific pattern, given that enhanced vulnerability was most strongly developed in the CD4 + T-cell subtype. In this paradigm, sporadic risk factors revealed the highest impact on cell type-specific sensitivity of CD4 + T cells to apoptosis. In contrast, normal aging results in an increased susceptibility to apoptosis of both, CD4 + and CD8 + T cells.

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Section: Neuromolecular Medicinementioning

confidence: 97%

Section: Neuromolecular Medicinementioning

confidence: 99%

Section: Neuromolecular Medicinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease

Schindowski

Kratzsch

Peters

et al. 2003

NMM

View full text Add to dashboard Cite

show abstract

“…However, this does not necessarily mean that the source of the Ca 2+ increase during the oscillation is extracellular, rather than intracellular, since the so-called capacitive entry of Ca 2+ from the extracellular space through a specific channel is indispensable for the refilling of intracellular store sites (23) ] i oscillation are now under investigation.…”

Section: +mentioning

confidence: 99%

Expression of Group I Metabotropic Glutamate Receptors in Rat Hippocampal Cells in Culture and Their Characterization by Intracellular Calcium Ion Dynamics

et al. 2003

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Abstract. The distribution of group I metabotropic glutamate receptors in rat hippocampal cells in culture was examined by calcium imaging and immunocytochemistry. To distinguish different cell types in the culture, the effects of t-ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid) and of NMDA (N-methyl-D-aspartate) were examined. ] i increase during NMDA administration did not show any oscillatory response to t-ACPD. After pharmacological examination using those two agonists, the cultured cells were subjected to immunocytochemistry using anti-GFAP and ant-MAP-2 antibodies to distinguish, respectively, astrocytes and neurons. All cells responding to NMDA with a sustained [Ca 2+ ] i increase were MAP-2-positive, whereas all cells showing either oscillatory or sustained [Ca 2+ ] i increase in response to t-ACPD were GFAP-positive. The present results show that, in these cultures, group I metabotropic glutamate receptors are mainly expressed on glial cells and contribute to dynamic [Ca 2+ ] i changes in astrocytes.

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Cardiovascular‐specific PSEN1 deletion leads to abnormalities in calcium homeostasis

Song

Zhao

Yang

et al. 2022

Cell Biology International

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Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees. Understanding the effects and mechanisms of PSEN1 in cardiomyocytes might have important implications for treatment of heart diseases. Here, we showed that PSEN1 was downregulated in ischemia‐induced failing hearts. Functionally, cardiovascular specific PSEN1 deletion led to spontaneous death of the mice due to cardiomyopathy. At the age of 11 months, the ratio of the heart weight/body weight was slightly lower in the Sm22a‐PSEN1‐KO mice compared with that of the WT mice. Echocardiography showed that the percentage of ejection fraction and fractional shortening was significantly reduced in the Sm22a‐PSEN1‐KO group compared with the percent of these measures in the WT group, indicating that PSEN1‐KO resulted in heart failure. The abnormally regulated genes resulted from PSEN1‐KO were detected to be enriched in muscle development and dilated cardiomyopathy. Among them, several genes encode Ca2+ ion channels, promoting us to investigate the effects of PSEN1 KO on regulation of Ca2+ in isolated adult cardiomyocytes. Consistently, in isolated adult cardiomyocytes, PSEN1‐KO increased the concentration of cytosolic Ca2+ and reduced Ca2+ concentration inside the sarcoplasmic reticulum (SR) lumen at the resting stage. Additionally, SR Ca2+ was decreased in the failing hearts of WT mice, but with the lowest levels observed in the failing hearts of PSEN1 knockout mice. These results indicate that the process of Ca2+ release from SR into cytoplasm was affected by PSEN1 KO. Therefore, the abnormalities in Ca2+ homeostasis resulted from downregulation of PSEN1 in failing hearts might contribute to aging‐related cardiomyopathy, which might had important implications for the treatment of aging‐related heart diseases.

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Presenilin mutations and calcium signaling defects in the nervous and immune systems

Cited by 59 publications

References 93 publications

Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease

Impact of Aging: Sporadic, and Genetic Risk Factors on Vulnerability to Apoptosis in Alzheimer's Disease

Expression of Group I Metabotropic Glutamate Receptors in Rat Hippocampal Cells in Culture and Their Characterization by Intracellular Calcium Ion Dynamics

Cardiovascular‐specific PSEN1 deletion leads to abnormalities in calcium homeostasis

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