更新于：2024-11-01

Tau tubulin kinase (TTBK) family x GSK-3β

更新于：2024-11-01

基本信息

关联

项与 Tau tubulin kinase (TTBK) family x GSK-3β 相关的药物

SAR-502250

靶点

GSK-3β

作用机制

GSK-3β抑制剂 [+1]

在研机构-

原研机构

Sanofi SA

在研适应症-

非在研适应症

阿尔茨海默症 [+2]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Tau tubulin kinase (TTBK) family x GSK-3β 相关的临床结果

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100 项与 Tau tubulin kinase (TTBK) family x GSK-3β 相关的转化医学

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0 项与 Tau tubulin kinase (TTBK) family x GSK-3β 相关的专利（医药）

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项与 Tau tubulin kinase (TTBK) family x GSK-3β 相关的文献（医药）

2024-05-01·Pflügers Archiv - European Journal of Physiology

Correction to: Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK‑3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high‑fat dietstreptozocin rat model

作者: Abdelrahman, Amany ; Mohammed, Sherine Ahmed ; Abdelhaliem, Nesreen G ; Hassan, Asmaa ; Moghazy, Hoda M

2024-05-01·Pflügers Archiv - European Journal of Physiology

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model

Article

作者: Abdelrahman, Amany ; Mohammed, Sherine Ahmed ; Abdelhaliem, Nesreen G ; Hassan, Asmaa ; Moghazy, Hoda M

AbstractThe American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-β deposition, glycogen synthase kinase 3 beta (GSK3β), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3β/TTBK1 pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10 weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200 μg/kg/day sc) or liraglutide (0.6 mg/kg/day sc) for 6 weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3β/TTBK1 expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.

2019-06-01·Journal of Cellular Biochemistry3区 · 生物学

miR‐219‐5p inhibits tau phosphorylation by targeting TTBK1 and GSK‐3β in Alzheimer's disease

3区 · 生物学

Article

作者: Tong, Qiuling ; Yi, Yanhong ; Chen, Weian ; Li, Jing

AbstractAs the most common neurodegenerative disease, Alzheimer's disease (AD) is characterized by memory, perception, and behavioral damage, which may ultimately lead to emotional fluctuation and even lethal delirium. Increasing studies indicate that microRNAs (miRNAs) are associated with pathological features of AD. However, the role of miR‐219‐5p in AD progression is still unclear. In this study, the functions of miR‐219‐5p were analyzed in vitro and in vivo. miR‐219‐5p was notably overexpressed in brain tissues of patients with AD. The overexpression of miR‐219‐5p activated the phosphorylation of Tau‐Ser198, Tau‐Ser199, Tau‐Ser201, and Tau‐Ser422. We further showed that miR‐219‐5p could mediate a decrease in the protein levels of tau‐tubulin kinase 1 (TTBK1) and glycogen synthase kinase 3β (GSK‐3β) by directly binding to their 3′‐untranslated region, thereby promoting the phosphorylation of tau in SH‐SY5Y Cells. Rescue experiments further revealed that the phosphorylation of tau‐mediated by miR‐219‐5p was dependent on the inhibition of TTBK1 and GSK‐3β. Moreover, suppressing the expression of both TTBK1 and GSK‐3β using miR‐219‐5p remarkably rescued AD‐like symptoms in amyloid precursor protein/presenilin 1 mice. Our findings indicate that the upregulation of TTBK1 and GSK‐3β mediated by the loss of miR‐219‐5p is a possible mechanism that contributes to tau phosphorylation and AD progression.