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  Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity.

Yagensky, O., Kohansal-Nodehi, M., Gunaseelan, S., Rabe, T., Zafar, S., Zerr, I., et al. (2019). Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity. eLife, 8: e47498. doi:10.7554/eLife.47498.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-9739-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-AC33-1
Genre: Journal Article

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 Creators:
Yagensky, O.1, Author              
Kohansal-Nodehi, M.2, Author              
Gunaseelan, S., Author
Rabe, T.3, Author              
Zafar, S., Author
Zerr, I., Author
Haertig, W., Author
Urlaub, H.4, Author              
Chua, J.1, Author              
Affiliations:
1Research Group of Protein Trafficking in Synaptic Development and Function, MPI for Biophysical Chemistry, Max Planck Society, ou_1933287              
2Department of Neurobiology, MPI for Biophysical Chemistry, Max Planck Society, ou_578595              
3Department of Genes and Behavior, MPI for Biophysical Chemistry, Max Planck Society, ou_persistent34              
4Research Group of Bioanalytical Mass Spectrometry, MPI for biophysical chemistry, Max Planck Society, ou_578613              

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Free keywords: human; mouse; neuroscience; rat
 Abstract: Alzheimer's disease is the most prevalent neurodegenerative disorder leading to progressive cognitive decline. Despite decades of research, understanding AD progression at the molecular level, especially at its early stages, remains elusive. Here, we identified several presymptomatic AD markers by investigating brain proteome changes over the course of neurodegeneration in a transgenic mouse model of AD (3×Tg-AD). We show that one of these markers, heme-binding protein 1 (Hebp1), is elevated in the brains of both 3×Tg-AD mice and patients affected by rapidly-progressing forms of AD. Hebp1, predominantly expressed in neurons, interacts with the mitochondrial contact site complex (MICOS) and exhibits a perimitochondrial localization. Strikingly, wildtype, but not Hebp1-deficient, neurons showed elevated cytotoxicity in response to heme-induced apoptosis. Increased survivability in Hebp1-deficient neurons is conferred by blocking the activation of the mitochondrial-associated caspase signaling pathway. Taken together, our data highlight a role of Hebp1 in progressive neuronal loss during AD progression.

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Language(s): eng - English
 Dates: 2019-08-27
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.7554/eLife.47498
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Title: eLife
Source Genre: Journal
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Pages: 33 Volume / Issue: 8 Sequence Number: e47498 Start / End Page: - Identifier: -