【摘 要】
:
In current drug discovery pipeline, in vitro biochemical and cell-based screening assays have been widely used before the validation tests in in vivo animal models.Nevertheless, the gap between two pl
【机 构】
:
Suzhou JoeKai Biotech LLC, Suzhou 215300, China S
【出 处】
:
中国神经科学学会第九届全国学术会议暨第五届会员代表大会
论文部分内容阅读
In current drug discovery pipeline, in vitro biochemical and cell-based screening assays have been widely used before the validation tests in in vivo animal models.Nevertheless, the gap between two platforms sometimes impairs the discovery progress, especially for the diseases with complicated mechanisms.In order to minimize such gap in the CNS disease area, we have developed several Drosophila models as supplementary approaches in parallel to the in vitro assays.These CNS fly models preserve behavioral deficits and pathological hallmarks similar to those observed in human patients, yet are low in running cost and are suitable for high-throughput screening expansions.The fly Alzheimers disease (AD) model was generated through targeted pan-neuronal expression of a transgene encoding a secretive form of human Aβ42 peptides in the Drosophila brain.Such expression leads to neurodegeneration with accumulation of Aβ42 and fibril deposits in the brain area, which may lead to shortened life span.In addition, AD flies also display severe age-dependent memory loss, highly mimicking dementia syndrome in AD patients.PC-controlled massive screening devices were utilize in the fly memory (T-maze) system, enabling screening of hundreds of compounds per day in scale for industrial needs.Fly model for NF1, Noonan syndrome were developed for drug screening service, along with other CNS disease models such as Parkinsons disease (PD), schizophrenia, and autism that have also been planned for the pipelines in CNS drug discovery.
其他文献
帕金森病(Parkinson,s Disease,PD)是一种中老年人常见的神经系统变性疾病,病理上主要表现为黑质(Substantia nigra)多巴胺(dopamine,DA)能神经元的丢失以及路易小体(Lewy Body)的形成.微管相关蛋白(Microtubule Associated Protein,MAPs)的非正常累积和聚集在神经变性疾病的发病中起到了重要作用.DJ-1/Park7
Objective Morphine is a potent analgesic.However, its clinical application is restricted due to morphine tolerance.The underlying mechanism is not fully understood.Glia are thought to be involved in m
Objective To explore the roles of liver x receptors (LXRs) and estrogen receptors (ERs) in the activation of microglia and astrocyte in the substantia nigra (SN) of the midbrain and its relationship w
Objective Death receptor 6 (DR6) is a death domain-containing receptor of the TNFR superfamily with an apparent regulatory function in hematopoietic and neuronal cells.Overexpression of DR6 in some ce
Objective Altered hippocampus is a valuable indicator of possible conversion from amnestic type mild cognitive impairment (aMCI) to Alzheimers disease (AD).However, little is known about the disrupted
Metallothioneins (MTs) have the potential to a variety of physiological processes, including neurobehavioral development, and cognitive functions.Here we further show that MTL-1 and MTL-2, metallothio
Objective Hydrogen sulfide (H2S) has been classified as a third novel gasotransmitter signaling molecule following nitric oxide and carbon monoxide.Accumulating evidence has shown that H2S produces ph
Cpne5 is a new Ca2+ dependent phospholipids binding protein.Our Previous studies on Cpne5 showed that it was mainly expressed in the ventricular zone (VZ).Further investigation demonstrated that Cpne5
Objective When food is available during a restricted and predictable time of the day, mammals exhibit food-anticipatory activity (FAA), a daily increase in locomotor activity preceding the presentatio
Aims The effect of experimental moderate pain induced by the tourniquet inflation around the upper limb on the recognition of pain-related words under controlled processing or automatic processing and