Disruption of endoplasmic reticulum-mitochondria tethering proteins in post-mortem Alzheimer's disease brain.

Neurobiology of Disease
Dawn H W LauChristopher C J Miller

Abstract

Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of key neuronal functions, many of which are perturbed in Alzheimer's disease. Moreover, damage to ER-mitochondria signaling is seen in cell and transgenic models of Alzheimer's disease. However, as yet there is little evidence that ER-mitochondria signaling is altered in human Alzheimer's disease brains. ER-mitochondria signaling is mediated by interactions between the integral ER protein VAPB and the outer mitochondrial membrane protein PTPIP51 which act to recruit and "tether" regions of ER to the mitochondrial surface. The VAPB-PTPIP51 tethers are now known to regulate a number of ER-mitochondria signaling functions including delivery of Ca2+from ER stores to mitochondria, mitochondrial ATP production, autophagy and synaptic activity. Here we investigate the VAPB-PTPIP51 tethers in post-mortem control and Alzheimer's disease brains. Quantification of ER-mitochondria signaling proteins by immunoblotting revealed loss of VAPB and PTPIP51 in cortex but not cerebellum at end-stage Alzheimer's disease. Proximity ligation assays were used to quantify the VAPB-PTPIP51 interaction in temporal cortex pyramidal neurons and cerebellar Purkinje cell ne...Continue Reading

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Citations

Sep 18, 2020·International Journal of Molecular Sciences·Sharmeelavathi KrishnanPrashant Bharadwaj
Dec 18, 2020·International Journal of Molecular Sciences·Fanny EysertMounia Chami
Jan 5, 2021·Frontiers in Cell and Developmental Biology·Hyunsu JungSeok-Kyu Kwon
Jan 15, 2021·Biomedicines·Simon M BellHeather Mortiboys
Nov 27, 2020·Frontiers in Neuroscience·Olesya M ShirokovaIrina V Mukhina
Mar 7, 2021·Biomedicines·Nuno Santos Leal, Luís Miguel Martins
Apr 21, 2021·Nature Neuroscience·Stephen M SmithLloyd T Elliott
Jul 2, 2021·Brain Pathology·Fumiaki MoriKoichi Wakabayashi
Oct 21, 2021·The FEBS Journal·Robert E Means, Samuel G Katz

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Methods Mentioned

BETA
transgenic
electrophoresis
protein concentration assay
electron
biopsy

Software Mentioned

Visiopharm
GraphPad
Excel
Prism

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