What question did this study set out to answer?

To identify the distinct enzymatic classes and cleavage specificities of the secretases responsible for generating the C-termini of amyloid beta-proteins Aβ1-40 and Aβ1-42.

April 1, 1999Journal of Neurochemistry

Distinct Secretases, a Cysteine Protease and a Serine Protease, Generate the C Termini of Amyloid β‐Proteins Aβ1‐40 and Aβ1‐42, Respectively

View Full Paper

Ask AI

Bookmark

To identify the distinct enzymatic classes and cleavage specificities of the secretases responsible for generating the C-termini of amyloid beta-proteins Aβ1-40 and Aβ1-42.
Treated amyloid precursor protein (APP)-transfected cell cultures, including cells carrying the Swedish mutation, with dipeptidyl aldehydes (Z-LL-CHO and Z-VL-CHO).
Applied the cysteine protease inhibitor E-64d and calpain inhibitor I to distinguish the mechanistic classes of gamma(40)- and gamma(42)-secretase.
Measured production of secreted Aβ1-40 and Aβ1-42 and assessed intracellular accumulation of precursor fragments.
E-64d treatment inhibited secreted Aβ1-40 generation with a concomitant accumulation of its precursor, while conversely increasing secreted Aβ1-42 production.
Calpain inhibitor I did not inhibit Aβ production, while dipeptidyl aldehyde treatment in Swedish mutant APP cultures shifted cleavage from the alpha-secretase site to the beta-secretase site.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Cell culture study demonstrates distinct enzymatic mechanisms generate amyloid beta-40 and beta-42, indicating separate cysteine and serine proteases compete for amyloid precursor protein.

Cite This Study

Figueiredo‐Pereira et al. (1999) studied this question.

synapsesocial.com/papers/6a86c2d8e0e6abca40d3b6e2 https://doi.org/10.1046/j.1471-4159.1999.721417.x

View Full Paper

Ask AI

Bookmark

Implication

Cell culture study demonstrates distinct enzymatic mechanisms generate amyloid beta-40 and beta-42, indicating separate cysteine and serine proteases compete for amyloid precursor protein.

Distinct Secretases, a Cysteine Protease and a Serine Protease, Generate the C Termini of Amyloid β‐Proteins Aβ1‐40 and Aβ1‐42, Respectively

Key Points

Discussion

Implication

Cite This Study

Distinct Secretases, a Cysteine Protease and a Serine Protease, Generate the C Termini of Amyloid β‐Proteins Aβ1‐40 and Aβ1‐42, Respectively

Key Points

Discussion

Implication

Cite This Study

Also Consider

Also Consider