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Advanced Glycation End Products Modulate Amyloidogenic APP Processing and Tau Phosphorylation: A Mechanistic Link between Glycation and the Development of Alzheimer’s Disease.


Maximus Peto’s Commentary

This looks like an interesting link between AGE-RAGE and Abeta1-42 and pTau in human Alzheimer’s brains.


Advanced Glycation End Products Modulate Amyloidogenic APP Processing and Tau Phosphorylation: A Mechanistic Link between Glycation and the Development of Alzheimer’s Disease.
ACS Chem Neurosci. 2018 May 16;9(5):988-1000.
Batkulwar K, Godbole R, Banarjee R, Kassaar O, Williams RJ, Kulkarni MJ
DOI: 10.1021/acschemneuro.7b00410
PubMed publication date (edat): 2/1/2018

Abstract

Advanced glycation end products (AGEs) are implicated in the pathology of Alzheimer’s disease (AD), as they induce neurodegeneration following interaction with the receptor for AGE (RAGE). This study aimed to establish a mechanistic link between AGE-RAGE signaling and AD pathology. AGE-induced changes in the neuro2a proteome were monitored by SWATH-MS. Western blotting and cell-based reporter assays were used to investigate AGE-RAGE regulated APP processing and tau phosphorylation in primary cortical neurons. Selected protein expression was validated in brain samples affected by AD. The AGE-RAGE axis altered proteome included increased expression of cathepsin B and asparagine endopeptidase (AEP), which mediated an increase in Aβ1-42 formation and tau phosphorylation, respectively. Elevated cathepsin B, AEP, RAGE, and pTau levels were found in human AD brain, coincident with enhanced AGEs. This study demonstrates that the AGE-RAGE axis regulates Aβ1-42 formation and tau phosphorylation via increased cathepsin B and AEP, providing a new molecular link between AGEs and AD pathology.

PMID: 29384651
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Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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