AAK1
- Known as:
- AAK1
- Catalog number:
- 000870A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- AAK1
Related genes to: AAK1
- Gene:
- AAK1 NIH gene
- Name:
- AP2 associated kinase 1
- Previous symbol:
- -
- Synonyms:
- KIAA1048, DKFZp686K16132
- Chromosome:
- 2p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-21
- Date modifiied:
- 2015-08-24
Related products to: AAK1
Related articles to: AAK1
- Defective intestinal epithelial tight junction (TJ) barrier function and endoplasmic reticulum (ER) stress are central pathological features of inflammatory bowel disease (IBD), yet the molecular mechanisms ER stress to TJ disruption remains poorly understood. Here, we investigated the role of autophagy in regulating intestinal TJ homeostasis during ER stress. ER stress was elevated in inflamed Crohn's disease tissue and chronic dextran sulfate sodium (DSS) colitis. In human intestinal epithelial Caco-2 monolayers, murine colon, and human colonic explants, induction of ER stress with tunicamycin, thapsigargin, or brefeldin A disrupted TJ barrier integrity, as demonstrated by reduced transepithelial electrical resistance and increased paracellular permeability. ER stress selectively increased the pore-forming TJ protein claudin-2 and altered occludin localization without significantly affecting other claudins. Pharmacologic activation of autophagy with rapamycin attenuated ER stress, restored TJ barrier function, reduced claudin-2 accumulation, and preserved occludin localization. Conversely, CRISPR-Cas9-mediated deletion of autophagy gene ATG7 exacerbated ER stress, apoptosis, and TJ barrier dysfunction in vitro, while intestinal epithelial-specific Atg7 knockout mice exhibited enhanced ER stress-induced intestinal permeability in-vivo. Mechanistically, prolonged ER stress impaired autophagic flux through IRE1α kinase signaling, resulting in accumulation of p62 and claudin-2. Inhibition of IRE1α kinase activity restored autophagy, reduced claudin-2 levels, and preserved TJ barrier function. We further identified adaptor-associated kinase 1 (AAK1) as a downstream mediator of IRE1α signaling during ER stress, with increased AP2M1 phosphorylation and altered claudin-2 trafficking. Claudin-2 overexpression alone induced ER stress and lysosomal damage, suggesting a feed-forward mechanism amplifying epithelial injury. Finally, enteric rapamycin administration reduced ER stress and restored autophagy in murine DSS colitis. Collectively, these findings identify an IRE1α-AAK1-autophagy axis as a critical regulator of intestinal TJ barrier integrity during ER stress. - Source: PubMed
Publication date: 2026/07/20
Arumugam PriyaSaha KushalGanapathy Ashwinkumar SubrameniumWang AlexandraHarris LeonardYochum GregoryNighot Prashant - To screen the potential core targets of (2S)-2'-Methoxykurarinone, a dimethyldihydroflavonoid derived from Sophora flavescens, against sepsis. Furthermore, we explore the in vivo pharmacological efficacy and potential mechanism of action through bioinformatics analysis, clinical sample verification, and an LPS-induced zebrafish sepsis model, aiming to provide experimental evidence for the development of this compound as a candidate lead compound against sepsis. - Source: PubMed
Publication date: 2026/07/28
Deng YaxingWang ChenglinJin YantongHu YingchunXu Yan - Alzheimer's disease (AD) is an aging-related neurodegenerative disease characterized by an initial memory impairment that progresses to a widespread cerebrocortical failure, culminating in death. Understanding the molecular mechanisms that protect brain function during aging may help reveal novel targets for the development of effective treatments for the memory and cognitive deficits associated with AD. In this study, we analyzed a gene expression dataset generated from the prefrontal cortices of individuals showing no neurological or cognitive abnormalities. The gene expression profiles were used to identify candidate protective genes. We then compared the expression patterns of these genes in aging with their expression patterns in AD, thereby enabling us to pinpoint the genes that potentially contribute to brain resilience that delays or prevents aging-related dementia. We selected seven genes that are potentially protective for aging and AD, and have known homologues in (). Among these genes, , , and were previously implicated in attenuating AD-related cognitive decline. Our experiments demonstrated that all seven genes prioritized by our resilience model significantly extended the lifespan of . Given the important relationship between neuronal functional integrity and lifespan (i.e., lifespan vs. brain health span), this work suggests the predicted AD resilience genes could serve as important candidate targets for therapeutic intervention. - Source: PubMed
Publication date: 2026/07/06
Guo LeiGrimaldi NicholasWang MinghuiHo LapShackleton BenNeff RyanWang ErmingTu ZhidongGandy SamHaroutunian VahramEhrlich Michelle EMobbs CharlesZhang Bin - This study aims to investigate the efficacy of drug repurposing using a corneal organoid model developed from patient-derived iPSCs and to elucidate the pathophysiology of Aniridia-Associated Keratopathy (AAK). - Source: PubMed
Publication date: 2026/07/14
Koc Ali CanKocak GamzeKahveci BurakMardinoglu AdilKarakülah GökhanUtine Canan AslıGüven Sinan - Chronic itch is a major burden, impacting the quality of life for one in four adults, and is closely associated with increased levels of anxiety, depression, and suicide. Despite its widespread burden, the precise mechanisms driving and sustaining chronic itch remain poorly understood. Non-histaminergic itch transmission in the spinal cord relies on the synaptic vesicle (SV) release of gastrin-releasing peptide (GRP) and the subsequent binding to the Gastrin-Releasing Peptide Receptor (GRPR). While SV exocytosis facilitates neurotransmitter release, such as GRP, SV endocytosis, mediated by key proteins including clathrin, adaptor associated kinase 1 (AAK1), and Dynamin (Dnm) are essential for retrieving and recycling SV from the presynaptic membrane to maintain signaling. Building upon evidence that AAK1- and Dnm-mediated endocytosis are viable targets to reverse pain, we characterized the role of these endocytic mediators in the regulation of synaptic transmission in itch pathways. - Source: PubMed
Publication date: 2026/06/29
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