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Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction

Einar Krogsaeter, Justin McKetney, Leopoldo Valiente‐Banuet, Angelica Marquez, Alexandra R. Willis, Zeynep Cakir, Erica Stevenson, Gwendolyn Μ. Jang, Antara Rao, Emmy Li, Anton Zhou, Anjani Attili, Timothy S. Chang, Martin Kampmann, Yadong Huang, Nevan J. Krogan, Danielle L. Swaney

2025Autophagy7 citationsDOIOpen Access PDF

Abstract

: Aβ-β-amyloid; AD-Alzheimer disease; APMS-affinity purification mass spectrometry; APOE-apolipoprotein E; APP-amyloid beta precursor protein; BafA1-bafilomycin A1; CMA-chaperone-mediated autophagy; COP-coatomer; ER-endoplasmic reticulum; ERAD-endoplasmic reticulum-associated degradation; ERGIC-endoplasmic reticulum-Golgi intermediate compartment; FCCP-carbonyl cyanide p-trifluoromethoxyphenylhydrazone; GABA-gamma-aminobutyric acid; GFP-green fluorescent protein; GPI-glycerophosphoinositol; GPN-glycyl-L-phenylalanine 2-naphthylamide; HA-hemagglutinin protein tag; iPSC-induced pluripotent stem cells; LAMP1-lysosomal associated membrane protein 1; LGALS3BP-galectin 3 binding protein; LysoIP-lysosomal immunoprecipitation; MAPT-microtubule associated protein tau; MR-CTSB-magic red cathepsin B; MS-mass spectrometry; NFT-neurofibrillary tangles; PCA-principal component analysis; PLA-proximity ligation assay; PSEN1-presenilin 1; PSEN2-presenilin 2; p-MAPT/Tau-phospho-MAPT/tau; ROS-reactive oxygen species; RT-qPCR-reverse transcriptase quantitative polymerase chain reaction; SEM-standard error of the mean; siRNA-short interfering RNA; SRCR-scavenger receptor cysteine-rich domain; TMED-transmembrane p24 trafficking protein; TMEM192-transmembrane protein 192.

Topics & Concepts

BiologyLysosomeCell biologyTFEBCathepsin DMannose 6-phosphate receptorLysosomal storage diseaseCathepsinEndosomeNeurodegenerationProteostasisAutophagyProteomicsTransport proteinApolipoprotein EProteomeFrontotemporal lobar degenerationCellCell cultureNiemann–Pick diseaseHuntington's diseaseProtein turnoverHEK 293 cellsFunction (biology)RabBiochemistryMembrane proteinTSG101Programmed cell deathProtein degradationCathepsin ANeuronal ceroid lipofuscinosisDownregulation and upregulationCellular transport and secretionCalcium signaling and nucleotide metabolismAlzheimer's disease research and treatments
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