Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease DOI
Dale D. O. Martin, Shaun S. Sanders

Biochemical Society Transactions, Год журнала: 2024, Номер 52(3), С. 1385 - 1392

Опубликована: Май 2, 2024

Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes the dynamic addition saturated fatty acids proteins, process known as S-acylation. With advent new techniques study S-acylation recent discovery enzymes that facilitate protein deacylation, novel small molecules are emerging potential therapeutic treatments. Huntington disease (HD) devastating, fatal neurodegenerative characterized by motor, cognitive, psychiatric deficits caused CAG repeat expansion HTT gene. The mutated HD, huntingtin, less S-acylated which associated with mutant aggregation cytotoxicity. Recent exciting findings indicate restoring HD models using molecule inhibitors deacylation protective. Herein, we set out describe roles how it can be targeted for design.

Язык: Английский

Mechanisms and functions of protein S-acylation DOI
Francisco S. Mesquita, Laurence Abrami, Maurine E. Linder

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(6), С. 488 - 509

Опубликована: Фев. 14, 2024

Язык: Английский

Процитировано

50
Altered Protein Palmitoylation as Disease Mechanism in Neurodegenerative Disorders DOI
Jakub Włodarczyk, Raja Bhattacharyya, Kim Doré

и другие.

Journal of Neuroscience, Год журнала: 2024, Номер 44(40), С. e1225242024 - e1225242024

Опубликована: Окт. 2, 2024

Palmitoylation, a lipid-based posttranslational protein modification, plays crucial role in regulating various aspects of neuronal function through altering membrane-targeting, stabilities, and protein–protein interaction profiles. Disruption palmitoylation has recently garnered attention as disease mechanism neurodegeneration. Many proteins implicated neurodegenerative diseases associated dysfunction, including but not limited to amyloid precursor protein, β-secretase (BACE1), postsynaptic density 95, Fyn, synaptotagmin-11, mutant huntingtin, superoxide dismutase 1, undergo palmitoylation, recent evidence suggests that altered contributes the pathological characteristics these disruption cellular processes. In addition, dysfunction enzymes catalyze depalmitoylation been connected development neurological disorders. This review highlights some latest advances our understanding regulation explores potential therapeutic implications.

Язык: Английский

Процитировано

5
Metformin exerted tumoricidal effects on colon cancer tumoroids via the regulation of autophagy pathway DOI Creative Commons

Roya Shabkhizan,

Çığır Biray Avcı, Sanya Haiaty

и другие.

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 4, 2025

Despite the existence of promising outcomes from standard 2D culture systems, these data are not completely akin to in vivo tumor parenchyma. Therefore, development and fabrication various 3D systems can part mimic intricate cell-to-cell interaction within real mass. Here, we aimed evaluate tumoricidal impacts metformin (MTF) on colorectal cancer (CRC) tumoroids an vitro system via modulation autophagy. CRC were developed using human umbilical vein endothelial cells (HUVECs), adenocarcinoma HT29 cells, fibroblasts (HFFF2) a ratio 1: 2: 1 2.5% methylcellulose. Tumoroids exposed different concentrations MTF, ranging 20 1000 mM, for 72 h. The survival rate was detected LDH release assay. expression protein levels autophagy-related factors measured PCR array western blotting, respectively. Using H & E, immunofluorescence staining (Ki-67), integrity proliferation examined. current protocol yielded typical compact with dark central region. slight changes released contents, no statistically significant differences achieved terms cell toxicity MTF-exposed groups compared control tumoroids, indicating insufficiency MTF induction death (p > 0.05). Western blotting indicated that LC3II/I reduced 120 mM < These coincided reduction intracellular p62 content mM-treated 40 analysis confirmed up-regulation, down-regulation several genes related signaling transduction pathways associated autophagy machinery shared effectors between apoptosis non-treated group more prominent incubated MTF. Histological examination loosening MTF-treated groups, especially increase (chromatin marginalization) necrotic (pyknotic nuclei) changes. In group, spindle-shaped remnants fibrillar matrix detected. Data proliferating Ki-67+ by increasing concentration mM. Different autophagy/apoptosis modulated after treatment coinciding both apoptotic tumoroid structure. inhibit dose-dependent manner.

Язык: Английский

Процитировано

0
The emerging roles of S-acylation in autophagy DOI

Jia Yao,

Chunyang Xie,

Aimin Yang

и другие.

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Let's get fat: emergence of S-acylation as a therapeutic target in Huntington disease DOI
Dale D. O. Martin, Shaun S. Sanders

Biochemical Society Transactions, Год журнала: 2024, Номер 52(3), С. 1385 - 1392

Опубликована: Май 2, 2024

Protein mislocalization is a key initial step in neurodegeneration, regardless of etiology, and has been linked to changes the dynamic addition saturated fatty acids proteins, process known as S-acylation. With advent new techniques study S-acylation recent discovery enzymes that facilitate protein deacylation, novel small molecules are emerging potential therapeutic treatments. Huntington disease (HD) devastating, fatal neurodegenerative characterized by motor, cognitive, psychiatric deficits caused CAG repeat expansion HTT gene. The mutated HD, huntingtin, less S-acylated which associated with mutant aggregation cytotoxicity. Recent exciting findings indicate restoring HD models using molecule inhibitors deacylation protective. Herein, we set out describe roles how it can be targeted for design.

Язык: Английский

Процитировано

1