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Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease

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translational Neurodegeneration 2019年第1期8卷 63-76页

作者： Zhi Dong Zhou Thevapriya Selvaratnam Ji Chao Tristan Lee Yin Xia Chao Eng-King Tan Department of Research National Neuroscience Institute11 Jalan Tan Tock SengSingapore 308433Singapore Department of Neurology Singapore General HospitalOutram RoadSingapore 169608Singapore Signature Research Program in Neuroscience and Behavioural Disorders Duke-NUS Medical School Singapore8 College RoadSingaporeSingapore

Parkinson’s disease(PD)is the most common neurodegenerative movement disorder,which is characterized by the progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta concomitant with Lewy body formation in affected brain *** detailed pathogenic mechanisms underlying the selective loss of dopaminergic neurons in PD are unclear,and no drugs or treatments have been developed to alleviate progressive dopaminergic neuron degeneration in ***,the formation ofα-synuclein-positive protein aggregates in Lewy body has been identified as a common pathological feature of PD,possibly stemming from the consequence of protein misfolding and dysfunctional *** is the mechanism for maintaining protein homeostasis via modulation of protein translation,enhancement of chaperone capacity and the prompt clearance of misfolded protein by the ubiquitin proteasome system and *** protein translation and impaired capacities of chaperone or protein degradation can disturb proteostasis processes,leading to pathological protein aggregation and neurodegeneration in *** recent years,multiple molecular targets in the modulation of protein translation vital to proteostasis and dopaminergic neuron degeneration have been *** potential pathophysiological and therapeutic significance of these molecular targets to neurodegeneration in PD is highlighted.

关键词： Molecular targets Neuron degeneration Parkinson’s disease protein aggregation protein translation Proteostasis

The Gelation of CAG Repeat Expansion RNAs Suppresses Global protein translation

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The Gelation of CAG Repeat Expansion RNAs Suppresses Global ...

Tbx 4 and Tbx 5 gene expression associated with appendage development and its relationship with the absence of the pelvic fin in Pampus argenteus

2021年全国生物相分离和相变学术研讨会

作者： Yuyin Pan Junmei Lu Boxun Lu School of Life Sciences Fudan University

RNA molecules with the expanded CAG repeat（eCAGr） undergo liquid-to-gel phase transitions rapidly,but the nuclear eCAGr RNA foci display liquid-like properties,different from their gel-like behaviour in *** functional impact of this RNA gelation is also completely *** we demonstrate that eCAGr RNA may form gel-like foci in the cytoplasm that are rapidly degraded by the *** RNA foci may lead to a drastic reduction of the global protein synthesis rate in cells and in vitro,possibly by sequestering the key protein translation elongation factor EEF2,which forms puncta colocalizing or surrounding the eCAGr RNA *** the eCAGr RNA gelation partially restored the global protein translation rate whereas the induction of enhanced gelation by an optogenetic system further exacerbated this ***,EEF2 puncta were significantly enhanced in brain slices from a mouse model and patients of Huntington’s disease,which is a CAG expansion disorder expressing *** study demonstrates the RNA gelation inside the cells and reveals its functional impact,providing new angles for understanding pathological mechanisms of repeat expansion diseases and global protein translation regulation..

关键词： CAG expansion protein translation autophagy

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Journal of Oceanology and Limnology 2024年第2期42卷 580-593页

作者： Shun ZHANG Xiaojing ZHU Lingzhu HU Kai LIAO Shanliang XU Danli WANG Chunyang GUO School of Marine Science Ningbo UniversityNingbo 315211China Key Laboratory of Applied Marine Biotechnology Ningbo UniversityChinese Ministry of EducationNingbo 315211China

The Tbx family is first known through the study of their functions in the body and limbs,and its members Tbx4 and Tbx5 genes are important factors in determining the characteristics of the *** argenteus is one of the important economical marine fishes widely distributed in offshore ***,it is necessary to study the role of Tbx family genes in the deletion of pelvic fin in *** this study,we cloned Tbx4 and Tbx5 cDNA sequence of ***(GenBank:MH709128 and MH712458).The Western blot and real time PCR were used to detect the expressions of Tbx4 and Tbx5 in different developmental stages and tissues of *** addition,whole-mount in-situ hybridization was used to study the localization of Tbx4 and Tbx5 genes in different developmental stages of *** show that the translation of Tbx4 mRNA was inhibited during the critical period of pelvic fin *** different tissues,Tbx4 protein levels were the lowest in the abdominal epithelium,and even lower than that in the pectoral fin,suggesting that the protein expression was also inhibited in the abdominal epithelium of adult ***,the results indicated that upstream genes regulation led to the key stage-specific and low expression of Tbx4 during pelvic fin development and in the abdominal epithelium.

关键词： Stromateidae pelvic fin protein translation T-box aquaculture broodstock

protein synthesis,degradation,and energy metabolism in T cell immunity

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Cellular & Molecular Immunology 2022年第3期19卷 303-315页

作者： Julia M.Marchingo Doreen A.Cantrell Cell Signalling and Immunology Division School of Life SciencesUniversity of DundeeDundeeDD15EHUK

T cell activation,proliferation,and differentiation into effector and memory states involve massive remodeling of T cell size and molecular content and create a massive increase in demand for energy and amino *** synthesis is an energy-and resource-demanding process;as such,changes in T cell energy production are intrinsically linked to proteome *** this review,we discuss how protein synthesis and degradation change over the course of a T cell immune response and the crosstalk between these processes and T cell energy *** highlight how the use of high-resolution mass spectrometry to analyze T cell proteomes can improve our understanding of how these processes are regulated.

关键词： T lymphocyte protein translation Proteomics Immunometabolism protein degradation

Glycogen synthase kinase 3 signaling in neural regeneration in vivo

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Journal of Molecular Cell Biology 2023年第12期15卷 1-11页

作者： Jing Zhang Shu-Guang Yang Feng-Quan Zhou Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310016China

Glycogen synthase kinase 3(GSK3)signaling plays important and broad roles in regulating neural development in vitro and in ***,we reviewed recent findings of GSK3-regulated axon regeneration in vivo in both the peripheral and central nervous systems and discussed a few controversial findings in the ***,current evidence indicates that GSK3βsignaling serves as an important downstream mediator of the PI3K–AKT pathway to regulate axon regeneration in parallel with the mTORC1 ***,the mTORC1 pathway supports axon regeneration mainly through its role in regulating cap-dependent protein translation,whereas GSK3βsignaling might be involved in regulating N6-methyladenosine mRNA methylation-mediated,cap-independent protein *** addition,GSK3 signaling also plays a key role in reshaping the neuronal transcriptomic landscape during ***,we proposed some research directions to further elucidate the molecular mechanisms underlying the regulatory function of GSK3 signaling and discover novel GSK3 signaling-related therapeutic ***,we hope to provide an updated and insightful overview of how GSK3 signaling regulates neural regeneration in vivo.

关键词： GSK3 neural regeneration protein translation gene transcription

The emerging roles of microRNAs in the molecular responses of metabolic rate depression

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分子细胞生物学报:英文版 2011年第3期3卷 167-175页

作者： Kyle K.Biggar Kenneth B.Storey Institute of Biochemistry and Department of Biology Carleton University1125 Colonel By DriveOttawaONCanada K1S 5B6

Metabolic rate depression is an important survival strategy for many animal species and a common element of hibernation,torpor,estivation,anoxia and *** of the molecular mechanisms that regulate reversible transitions to and from hypometabolic states have identified principles of regulatory *** control mechanisms are conserved among biologically diverse organisms and include the coordinated reduction of specific groups of key regulatory enzymes or proteins in the cell,a process likely driven by microRNA target repression/*** present review focuses on a growing area of research in hypometabolism and mechanisms involving the rapid and reversible control of translation facilitated by *** analysis draws primarily from current research on three animal models:hibernating mammals,anoxic turtles and freeze-tolerant frogs(with selected examples from multiple other sources).Here,we demonstrate a link between metabolic rate depression,a well-documented response to periods of environmental stress,and microRNA ***-based expression profiles and PCR-driven studies have revealed that specific microRNAs are induced in response to environmental *** members of this group decrease pro-apoptotic signaling,reduce muscle wasting and reduce protein translation,whereas other members contribute to cell cycle arrest and mitogen-activated protein kinase *** of the same microRNAs are frequently deregulated in numerous disease pathologies and,hence,the hypometabolism model could provide a novel approach for the treatment of stroke and heart attack in humans.

关键词： microRNA metabolism metabolic rate depression protein translation muscle atrophy cell cycle apoptosis