Neuron-astrocyte transmitophagy is altered in Alzheimer's disease

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Lampinen , R , Belaya , I , Saveleva , L , Liddell , J R , Rait , D , Huuskonen , M T , Giniatullina , R , Sorvari , A , Soppela , L , Mikhailov , N , Boccuni , I , Giniatullin , R , Cruz-Haces , M , Konovalova , J , Koskuvi , M , Domanskyi , A , Hämäläinen , R H , Goldsteins , G , Koistinaho , J , Malm , T , Chew , S , Rilla , K , White , A R , Marsh-Armstrong , N & Kanninen , K M 2022 , ' Neuron-astrocyte transmitophagy is altered in Alzheimer's disease ' , Neurobiology of Disease , vol. 170 , 105753 .

Title: Neuron-astrocyte transmitophagy is altered in Alzheimer's disease
Author: Lampinen, Riikka; Belaya, Irina; Saveleva, Liudmila; Liddell, Jeffrey R.; Rait, Dzhessi; Huuskonen, Mikko T.; Giniatullina, Raisa; Sorvari, Annika; Soppela, Liisi; Mikhailov, Nikita; Boccuni, Isabella; Giniatullin, Rashid; Cruz-Haces, Marcela; Konovalova, Julia; Koskuvi, Marja; Domanskyi, Andrii; Hämäläinen, Riikka H.; Goldsteins, Gundars; Koistinaho, Jari; Malm, Tarja; Chew, Sweelin; Rilla, Kirsi; White, Anthony R.; Marsh-Armstrong, Nicholas; Kanninen, Katja M.
Contributor organization: Institute of Biotechnology
Neuroscience Center
Date: 2022-08
Language: eng
Number of pages: 13
Belongs to series: Neurobiology of Disease
ISSN: 0969-9961
Abstract: Under physiological conditions in vivo astrocytes internalize and degrade neuronal mitochondria in a process called transmitophagy. Mitophagy is widely reported to be impaired in neurodegeneration but it is unknown whether and how transmitophagy is altered in Alzheimer's disease (AD). Here we report that the internalization of neuronal mitochondria is significantly increased in astrocytes isolated from AD mouse brains. We also demonstrate that the degradation of neuronal mitochondria by astrocytes is increased in AD mice at the age of 6 months onwards. Furthermore, we demonstrate for the first time a similar phenomenon between human neurons and AD astrocytes, and in murine hippocampi in vivo. The results suggest the involvement of S100a4 in impaired mitochondrial transfer between neurons and AD astrocytes together with significant increases in the mitophagy regulator and reactive oxygen species in aged AD astrocytes. These findings demonstrate altered neuronsupporting functions of AD astrocytes and provide a starting point for studying the molecular mechanisms of transmitophagy in AD.
Subject: Alzheimer's disease
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: publishedVersion

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