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izvor podataka: crosbi

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 (CROSBI ID 313378)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

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 // Mechanisms of ageing and development, 207 (2022), 111726, 11. doi: 10.1016/j.mad.2022.111726

Podaci o odgovornosti

Dominko, Kristina ; Rastija, Ana ; Smiljanić, Kosara ; Mladenović, Aleksandra ; Lešnjaković, Lucija ; Kanazir, Selma ; Milanović, Desanka ; Hećimović, Silva

engleski

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

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.

amyloid-ß ; APP ; BACE1 ; ß-secretase ; Sez6 ; Sez6

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Podaci o izdanju

207

2022.

111726

11

objavljeno

0047-6374

1872-6216

10.1016/j.mad.2022.111726

Povezanost rada

Temeljne medicinske znanosti

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