Last update 19 Sep 2024

GANAB

Last update 19 Sep 2024

Basic Info

Synonyms

Alpha-glucosidase 2, G2AN, GANAB

+ [6]

Introduction

Catalytic subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for PKD1/Polycystin-1 and PKD2/Polycystin-2 maturation and localization to the cell surface and cilia (PubMed:27259053).

Drugs associated with GANAB

Prodrugs of IHVR-19029

Target

GANAB x α-glucosidase

Mechanism

GANAB inhibitors [+1]

Active Org.

Baruch S. Blumberg Institute

Originator Org.

Baruch S. Blumberg Institute

Active Indication

Hemorrhagic Fever, Ebola [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GANAB

100 Translational Medicine associated with GANAB

0 Patents (Medical) associated with GANAB

255

Literatures (Medical) associated with GANAB

01 Sep 2024·eBioMedicine

Exploring antidiabetic drug targets as potential disease-modifying agents in osteoarthritis

Article

Author: Jin, Xinzhong ; Si, Shucheng ; Oo, Win Min ; Zhang, Yan ; Li, Guangyi ; Zhang, Yuqing ; Boer, Cindy G ; Duong, Vicky ; Cai, Qianying ; Hunter, David J ; Wei, Xiaojuan ; Gao, Youshui ; Zheng, Xianyou ; Fu, Kai ; Zhang, Changqing

BACKGROUNDOsteoarthritis is a leading cause of disability, and disease-modifying osteoarthritis drugs (DMOADs) could represent a pivotal advancement in treatment. Identifying the potential of antidiabetic medications as DMOADs could impact patient care significantly.METHODSWe designed a comprehensive analysis pipeline involving two-sample Mendelian Randomization (MR) (genetic proxies for antidiabetic drug targets), summary-based MR (SMR) (for mRNA), and colocalisation (for drug-target genes) to assess their causal relationship with 12 osteoarthritis phenotypes. Summary statistics from the largest genome-wide association meta-analysis (GWAS) of osteoarthritis and gene expression data from the eQTLGen consortium were utilised.FINDINGSSeven out of eight major types of clinical antidiabetic medications were identified, resulting in fourteen potential drug targets. Sulfonylurea targets ABCC8/KCNJ11 were associated with increased osteoarthritis risk at any site (odds ratio (OR): 2.07, 95% confidence interval (CI): 1.50-2.84, P < 3 × 10^-4), while PPARG, influenced by thiazolidinediones (TZDs), was associated with decreased risk of hand (OR: 0.61, 95% CI: 0.48-0.76, P < 3 × 10^-4), finger (OR: 0.50, 95% CI: 0.35-0.73, P < 3 × 10^-4), and thumb (OR: 0.49, 95% CI: 0.34-0.71, P < 3 × 10^-4) osteoarthritis. Metformin and GLP1-RA, targeting GPD1 and GLP1R respectively, were associated with reduced risk of knee and finger osteoarthritis. In the SMR analyses, gene expression of KCNJ11, GANAB, ABCA1, and GSTP1, targeted by antidiabetic drugs, was significantly linked to at least one osteoarthritis phenotype and was replicated across at least two gene expression datasets. Additionally, increased KCNJ11 expression was related to decreased osteoarthritis risk and co-localised with at least one osteoarthritis phenotype.INTERPRETATIONOur findings suggest a potential therapeutic role for antidiabetic drugs in treating osteoarthritis. The results indicate that certain antidiabetic drug targets may modify disease progression, with implications for developing targeted DMOADs.FUNDINGThis study was funded by the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (2022), the Shanghai Municipal Health Commission Health Industry Clinical Research Project (Grant No. 20224Y0139), Beijing Natural Science Foundation (Grant No. 7244458), and the Postdoctoral Fellowship Program (Grade C) of China Postdoctoral Science Foundation (Grant No. GZC20230130).

01 Aug 2024·Kidney360

Genetic Analysis of Severe Polycystic Liver Disease in Japan

Article

Author: Sawa, Naoki ; Besse, Whitney ; Hoshino, Junichi ; Kurihara, Shigekazu ; Oba, Yuki ; Somlo, Stefan ; Suwabe, Tatsuya ; Yamanouchi, Masayuki ; Mizuno, Hiroki ; Long, Kelly T. ; Sekine, Akinari ; Hasegawa, Eiko ; Ubara, Yoshifumi

Key Points

Among patients with severe polycystic liver disease (PLD) (height-adjusted total liver volume of <1800 ml/m), PKD2 variants were found in 34%.

Three patients with PKD1 or PKD2 variants are reported with severe PLD but normal-sized kidneys (hTKV of < 250 ml/m).

BackgroundPolycystic liver disease (PLD) is present in most patients with autosomal dominant polycystic kidney disease (ADPKD). PLD can alternatively be found with few, if any, kidney cysts as a diagnosis of isolated PLD (autosomal dominant PLD [ADPLD]). Several genes are identified as causative for this spectrum of phenotypes; however, the relative incidence of genetic etiologies among patients with severe PLD is unknown.MethodsPatients with ADPKD or ADPLD having severe PLD defined as height-adjusted total liver volume (hTLV) >1800 ml/m were recruited. Subsequent clinical care was followed. Genetic analysis was performed using whole exome sequencing.ResultsWe enrolled and sequenced 49 patients (38 women, 11 men). Pathogenic or suspected pathogenic variants in polycystic disease genes were found in 44 of 49 patients (90%). The disease gene was PKD1 in 20 of 44 patients (45%), PKD2 in 15 of 44 patients (34%), PRKCSH in 5 of 44 patients (11%), GANAB in 2 of 44 patients (5%), SEC63 in 1 of 44 patients (2%), and ALG8 in 1 of 44 patients (2%). The median hTLV was no different between genetically defined ADPKD and ADPLD groups (4431 [range, 1817–9148] versus 3437 [range, 1860–8211]) ml, P = 0.77), whereas height-adjusted kidney volume was larger as expected in ADPKD than in ADPLD (607 [range, 190–2842] versus 179 [range, 138–234] ml/m, P < 0.01). Of the clinically defined ADPKD patients, 20 of 38 patients (53%) were PKD1, 15 of 38 (39%) were PKD2, and 3 (8%) remained genetically unsolved. Among patients with a pathogenic PKD1 or PKD2 variant, we found three patients with a liver-dominant ADPKD (severe PLD with height-adjusted total kidney volume <250 ml/m).ConclusionsADPLD-related genes represent 20% of patients with severe PLD in our cohort. Of those enrolled with ADPKD, we observed a higher frequency of PKD2 carriers than in any previously reported ADPKD cohorts. Although there was no significant difference in the hTLV between patients with PKD1 and PKD2 in this cohort, our data suggest that enrollment on the basis of severe PLD may enrich for patients with PKD2.

01 Jul 2024·Biochemical and Biophysical Research Communications

α,β-trehalose, an intracellular substance in resting cyst of colpodid ciliates as a key to environmental tolerances

Article

Author: Saito, Yuta ; Ogata, Makoto ; Saito, Ryota ; Suizu, Futoshi ; Hakozaki, Shuntaro ; Watanabe, Kozo ; Sogame, Yoichiro ; Suzuki, Tomohiro

α,α-trehalose is a well-known sugar that plays a key role in establishing tolerance to environmental stresses in many organisms, except unicellular eukaryotes. However, almost nothing is known about α,β-trehalose, including their synthesis, function, and even presence in living organisms. In this study, we identified α,β-trehalose in the resting cyst, a dormancy cell form characterized by extreme tolerance to environmental stresses, of the ciliated protist Colpoda cucullus, using high-performance liquid chromatography (HPLC), and a proton nuclear magnetic resonance (¹H NMR). Gene expression analysis revealed that the expression of trehalose-6-phosphate synthase (TPS), glycosyltransferase (GT), alpha-amylase (AMY), and trehalose transporter 1 (TRET1), were up-regulated in encystment, while the expression of α-glucosidase 2 (AG2) and trehalase (TREH) was up-regulated in excystment. These results suggest that α,β-trehalose is synthesized during encystment process, while and contributes to extreme tolerances to environmental stressors, stored carbohydrates, and energy reserve during resting cyst and/or during excystment.

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GANAB

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