TY  - JOUR
AU  - Dominko, Kristina
AU  - Rastija, Ana
AU  - Smiljanić, Kosara
AU  - Mladenović, Aleksandra
AU  - Lešnjaković, Lucija
AU  - Kanazir, Selma
AU  - Milanović, Desanka
AU  - Hećimović, Silva
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0047637422001087
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5109
AB  - The formation of amyloid-ß peptides (Aß), that accumulate in Alzheimer's disease (AD) brains, involves proteolytic processing of the amyloid precursor protein (APP) firstly by ß-secretase (BACE1). Since BACE1 cleaves a plethora of other substrates, in this work we investigated whether the proteolysis and/or distribution of other BACE1 substrates, such as seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), is altered in AD. To test this we used 5xFAD mouse model brains that show an early accumulation of Aß plaques already at 2-months of age. Here we show for the first time that accumulation of BACE1 in peri-plaque regions and its enhanced levels in AD brains does not affect proteolysis of BACE1 substrates other than APP, such as Sez6 and Sez6L. We observed altered distribution of Sez6 and Sez6L in the area of Aß plaques in 5xFAD brains which is distinct to that of APP, BACE1 and/or LAMP1, suggesting different localization and/or function of these BACE1 substrates. While it is necessary to further elucidate the potential role that this may play in the course of AD, it is likely that Aß-targeted therapies may have beneficial effects against accumulation and/or altered distribution of BACE1 and its substrates, in addition to APP.
PB  - Clare: Elsevier Ireland Ltd.
T2  - Mechanisms of Ageing and Development
T1  - Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.
VL  - 207
DO  - 10.1016/j.mad.2022.111726
SP  - 111726
ER  - 

@article{
author = "Dominko, Kristina and Rastija, Ana and Smiljanić, Kosara and Mladenović, Aleksandra and Lešnjaković, Lucija and Kanazir, Selma and Milanović, Desanka and Hećimović, Silva",
year = "2022",
abstract = "The formation of amyloid-ß peptides (Aß), that accumulate in Alzheimer's disease (AD) brains, involves proteolytic processing of the amyloid precursor protein (APP) firstly by ß-secretase (BACE1). Since BACE1 cleaves a plethora of other substrates, in this work we investigated whether the proteolysis and/or distribution of other BACE1 substrates, such as seizure protein 6 (Sez6) and seizure 6-like protein (Sez6L), is altered in AD. To test this we used 5xFAD mouse model brains that show an early accumulation of Aß plaques already at 2-months of age. Here we show for the first time that accumulation of BACE1 in peri-plaque regions and its enhanced levels in AD brains does not affect proteolysis of BACE1 substrates other than APP, such as Sez6 and Sez6L. We observed altered distribution of Sez6 and Sez6L in the area of Aß plaques in 5xFAD brains which is distinct to that of APP, BACE1 and/or LAMP1, suggesting different localization and/or function of these BACE1 substrates. While it is necessary to further elucidate the potential role that this may play in the course of AD, it is likely that Aß-targeted therapies may have beneficial effects against accumulation and/or altered distribution of BACE1 and its substrates, in addition to APP.",
publisher = "Clare: Elsevier Ireland Ltd.",
journal = "Mechanisms of Ageing and Development",
title = "Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.",
volume = "207",
doi = "10.1016/j.mad.2022.111726",
pages = "111726"
}

Dominko, K., Rastija, A., Smiljanić, K., Mladenović, A., Lešnjaković, L., Kanazir, S., Milanović, D.,& Hećimović, S.. (2022). Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.. in Mechanisms of Ageing and Development
Clare: Elsevier Ireland Ltd.., 207, 111726.
https://doi.org/10.1016/j.mad.2022.111726

Dominko K, Rastija A, Smiljanić K, Mladenović A, Lešnjaković L, Kanazir S, Milanović D, Hećimović S. Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L.. in Mechanisms of Ageing and Development. 2022;207:111726.
doi:10.1016/j.mad.2022.111726 .

Dominko, Kristina, Rastija, Ana, Smiljanić, Kosara, Mladenović, Aleksandra, Lešnjaković, Lucija, Kanazir, Selma, Milanović, Desanka, Hećimović, Silva, "Amyloid-ß plaque formation and BACE1 accumulation in the brains of a 5xFAD Alzheimer's disease mouse model is associated with altered distribution and not proteolysis of BACE1 substrates Sez6 and Sez6L." in Mechanisms of Ageing and Development, 207 (2022):111726,
https://doi.org/10.1016/j.mad.2022.111726 . .