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Modulation of the e...
Modulation of the endoplasmic reticulum-mitochondria interface in Alzheimer's disease and related models
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Hedskog, Louise (author)
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- Pinho, Catarina Moreira (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Filadi, Riccardo (author)
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- Rönnbäck, Annica (author)
- Karolinska Institutet
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Hertwig, Laura (author)
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- Wiehager, Birgitta (author)
- Karolinska Institutet
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- Larssen, Pia (author)
- Karolinska Institutet
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- Gellhaar, Sandra (author)
- Karolinska Institutet
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- Sandebring, Anna (author)
- Karolinska Institutet
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- Westerlund, Marie (author)
- Karolinska Institutet
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- Graff, Caroline (author)
- Karolinska Institutet
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- Winblad, Bengt (author)
- Karolinska Institutet
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- Galter, Dagmar (author)
- Karolinska Institutet
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- Behbahani, Homira (author)
- Karolinska Institutet
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Pizzo, Paola (author)
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- Glaser, Elzbieta (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Ankarcrona, Maria (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2013-04-25
- 2013
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:19, s. 7916-7921
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Abstract
Subject headings
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- It is well-established that subcompartments of endoplasmic reticulum (ER) are in physical contact with the mitochondria. These lipid raft-like regions of ER are referred to as mitochondria-associated ER membranes (MAMs), and they play an important role in, for example, lipid synthesis, calcium homeostasis, and apoptotic signaling. Perturbation of MAM function has previously been suggested in Alzheimer's disease (AD) as shown in fibroblasts from AD patients and a neuroblastoma cell line containing familial presenilin-2 AD mutation. The effect of AD pathogenesis on the ER-mitochondria interplay in the brain has so far remained unknown. Here, we studied ER-mitochondria contacts in human AD brain and related AD mouse and neuronal cell models. We found uniform distribution of MAM in neurons. Phosphofurin acidic cluster sorting protein-2 and sigma 1 receptor, two MAM-associated proteins, were shown to be essential for neuronal survival, because siRNA knockdown resulted in degeneration. Up-regulated MAM-associated proteins were found in the AD brain and amyloid precursor protein (APP)(Swe/Lon) mouse model, in which up-regulation was observed before the appearance of plaques. By studying an ER-mitochondria bridging complex, inositol-1,4,5-triphosphate receptor-voltage-dependent anion channel, we revealed that nanomolar concentrations of amyloid beta-peptide increased inositol-1,4,5-triphosphate receptor and voltage-dependent anion channel protein expression and elevated the number of ER-mitochondria contact points and mitochondrial calcium concentrations. Our data suggest an important role of ER-mitochondria contacts and cross-talk in AD pathology.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- AD mouse models
- hippocampal neurons
- human cortical brain tissue
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hedskog, Louise
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Pinho, Catarina ...
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Filadi, Riccardo
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Rönnbäck, Annica
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Hertwig, Laura
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Wiehager, Birgit ...
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show more...
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Larssen, Pia
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Gellhaar, Sandra
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Sandebring, Anna
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Westerlund, Mari ...
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Graff, Caroline
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Winblad, Bengt
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Galter, Dagmar
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Behbahani, Homir ...
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Pizzo, Paola
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Glaser, Elzbieta
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Ankarcrona, Mari ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
- Articles in the publication
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Proceedings of t ...
- By the university
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Stockholm University
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Karolinska Institutet