APP palmitoylation is involved in the increase in Aβ1-42 induced by aluminum

Song, Jianliang; Yuan, Chunman; Li, Wenjing; Gao, Ting; Lu, Xiaoting; Wang, Linping

doi:10.1016/j.brainres.2021.147709

Cited by 5 publications

(1 citation statement)

References 35 publications

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“…The palmitoylation level of AMPARs was detected by IP-ABE assay which was performed in our previous research (Song et al 2022a, Song et al 2022b). The lysis buffer containing N-ethylmaleimide (NEM) solution (Sigma, USA) was used to extract the total proteins.…”

Section: Immunoprecipitation and Acyl-biotin Exchange (Ip-abe) Assaymentioning

confidence: 99%

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

Song

Yuan

et al. 2023

Environ Sci Pollut Res

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Aluminum (Al) is a neurotoxic substance associated with cognitive dysfunction and neurodegenerative diseases, such as Alzheimer's disease, but the mechanisms for aluminum neurotoxicity remain to be identi ed. In this work, we try to investigate a novel potential biomarker of cognitive dysfunction following aluminum exposure and the mechanism involved. Recently, miR-134-3p was reported as a novel regulator of cognitive function. To address this, we investigate the expression level of miR-134-3p in plasma from 280 aluminum factory workers and analyzed the correlation between miRNA-134-3p, blood Al concentration, and Montreal Cognitive Assessment Scale (MoCA scale) score. The results implied that occupational aluminum exposure elevated miR-134-3p expression in the plasma of workers accompanied by cognitive impairment. Our experiment studies using both animal models and PC12 cells validated the up-regulation of miR-134-3p caused by aluminum. In addition, we identi ed that palmitoylation enzyme zDHHC3 was the target of miR-134-3p, and the decreasing AMPAR receptors (AMPARs) tra cking was related to the learning and memory impairment induced by aluminum. More importantly, using transfection and interference approaches in PC12 cells, inhibition of miR-134-3p resulted in a recovery of zDHHC3-AMPARs axis to a certain extent in response to aluminum. In summary, miR-134-3p was found to be involved in aluminum neurotoxicity by targeting zDHHC3-AMPARs axis and could serve as a potential biomarker or helpful target.

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Section: Immunoprecipitation and Acyl-biotin Exchange (Ip-abe) Assaymentioning

confidence: 99%

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

Song

Yuan

et al. 2023

Environ Sci Pollut Res

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Stabilization of mitochondria‐associated endoplasmic reticulum membranes regulates Aβ generation in a three‐dimensional neural model of Alzheimer's disease

Zellmer,

Tarantino,

Kim

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONWe previously demonstrated that regulating mitochondria‐associated endoplasmic reticulum (ER) membranes (MAMs) affects axonal Aβ generation in a well‐characterized three‐dimensional (3D) neural Alzheimer's disease (AD) model. MAMs vary in thickness and length, impacting their functions. Here, we examined the effect of MAM thickness on Aβ in our 3D neural model of AD.METHODSWe employed fluorescence resonance energy transfer (FRET) or fluorescence‐based MAM stabilizers, electron microscopy, Aβ enzyme‐linked immunosorbent assay (ELISA), and live‐cell imaging with kymography to assess how stabilizing MAMs of different gap widths influence Aβ production and MAM axonal mobility.RESULTSStabilizing tight MAMs (∼6 nm gap width) significantly increased Aβ levels, whereas basal (∼25 nm) and loose MAMs (∼40 nm) maintained or reduced Aβ levels, respectively. Tight MAMs reduced mitochondrial axonal velocity compared to basal MAMs, while loose MAMs showed severely reduced axonal distribution.DISCUSSIONOur findings suggest that stabilizing MAMs of specific gap widths, particularly in axons, without complete destabilization could be an effective therapeutic strategy for AD.Highlights The stabilization of MAMs exacerbates or ameliorates Aβ generation from AD neurons in a MAM gap width‐dependent manner. A specific stabilization threshold within the MAM gap width spectrum shifts the amyloidogenic process to non‐amyloidogenic. Tight MAMs slow down mitochondrial axonal transport compared to lose MAMs offering a quantitative method for measuring MAM stabilization.

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APP lysine 612 lactylation ameliorates amyloid pathology and memory decline in Alzheimer’s disease

Tian,

Li,

et al. 2025

Journal of Clinical Investigation

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APP palmitoylation is involved in the increase in Aβ1-42 induced by aluminum

Cited by 5 publications

References 35 publications

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity

Stabilization of mitochondria‐associated endoplasmic reticulum membranes regulates Aβ generation in a three‐dimensional neural model of Alzheimer's disease

APP lysine 612 lactylation ameliorates amyloid pathology and memory decline in Alzheimer’s disease

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