| 1 | Alpha-synuclein gene structure,evolution,and protein aggregation显示文摘α-synuclein,a member of the synuclein family,is predominately expressed in brain tissues,where it is the major component of Lewy bodies,the major hallmark of Parkinson’s disease.We analyzed the phylogenetics,gene structure,and effects of different forms of α-synuclein on in vitro protein aggregation.The synuclein phylogenetic tree showed that sequences could be classified into α,β,and γ protein groups.The orthologous gene α-,βand γ-synuclein showed similar evolutionary distance to the paralogous gene α-,βand γ-synuclein.Bioinformatics analysis suggests that the amino-acid sequence of human α-synuclein can be divided into three regions: N-terminal amphipathic region (1–60),central hydrophobic non-amyloid beta component segment (61–95),and the C-terminal acidic part (96–140).The mutant site of A30P is at the second exon of α-synuclein,whereas E46K is located at the third exon of α-synuclein.α-synuclein alternative splicing results in four isomers,and five exons,all of which participate in protein coding,comprising 140 amino acids to produce the major α-synuclein in vivo.The three α-synuclein isoforms are products of alternative splicing,α-synuclein 126,112 and 98.We also review the genetic and cellular factors that affect the aggregation of α-synuclein and compounds that inhibit aggregation.A better understanding of α-synuclein sequences,structure,and function may allow better targeted therapy and diagnosis of α-synuclein in Parkinson’s disease and other neurodegenerative diseases. | Lili Xiong Peng Zhao Zhiyun Guo Jianhua Zhang Diqiang Li Canquan Mao | 2010 | Neural Regeneration Research2010，5，18： | 0 |
| 2 | Genome editing of PAR2 through targeted delivery of CRISPR-Cas9 system for alleviating acute lung inflammation via ERK/NLRP3/IL-1β and NO/iNOS signalling显示文摘Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases,immune cell infiltration and protease-driven tissue damages.It is an urgent need to explore potential drug strategies for mitigating lung inflammation.Protease-activated receptor 2(PAR2)as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction.However,it has been rarely reported about the role of PAR2 in lung inflammation.This study applied CRISPR-Cas9 system encoding Cas9 and sg RNA(p Cas9-PAR2)for PAR2 knockout and fabricated an anionic human serum albuminbased nanoparticles to deliver p Cas9-PAR2 with superior inflammation-targeting efficiency and stability(TAP/p Cas9-PAR2).TAP/p Cas9-PAR2 robustly facilitated p Cas9-PAR2 to enter and transfect inflammatory cells,eliciting precise gene editing of PAR2 in vitro and in vivo.Importantly,PAR2 deficiency by TAP/p Cas9-PAR2 effectively and safely promoted macrophage polarization,suppressed proinflammatory cytokine releases and alleviated acute lung inflammation,uncovering a novel value of PAR2.It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/p Cas9-PAR2was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/i NOS signalling.Therefore,this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases. | Xin Zhuo Yue Wu Xiujuan Fu Jianbin Li Yuxin Xiang Xiaoyu Liang Canquan Mao Yuhong Jiang | 2024 | Acta Pharmaceutica Sinica B2024，14，3： | 0 |
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