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51.
Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Heesun Choi Haeng Jun Kim Jinhee Yang Sehyun Chae Wonik Lee Sunwoo Chung Jisoo Kim Hyunjung Choi Hyeseung Song Chang Kon Lee Jae Hyun Jun Yong Jae Lee Kyunghyeon Lee Semi Kim Hye‐ri Sim Young Il Choi Keun Ho Ryu Jong‐Chan Park Dongjoon Lee Sun‐Ho Han Daehee Hwang Jangbeen Kyung Inhee Mook‐Jung 《Aging cell》2020,19(1)
Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice. 相似文献
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Loss of function of Arabidopsis NADP‐malic enzyme 1 results in enhanced tolerance to aluminum stress
54.
Fanny E. Hartmann Alodie Snirc Amandine Cornille Ccile God Pascal Touzet Fabienne Van Rossum Elisabeth Fournier Stphanie Le Prieur Jacqui Shykoff Tatiana Giraud 《Molecular ecology》2020,29(6):1154-1172
Study of the congruence of population genetic structure between hosts and pathogens gives important insights into their shared phylogeographical and coevolutionary histories. We studied the population genetic structure of castrating anther‐smut fungi (genus Microbotryum) and of their host plants, the Silene nutans species complex, and the morphologically and genetically closely related Silene italica, which can be found in sympatry. Phylogeographical population genetic structure related to persistence in separate glacial refugia has been recently revealed in the S. nutans plant species complex across Western Europe, identifying several distinct lineages. We genotyped 171 associated plant–pathogen pairs of anther‐smut fungi and their host plant individuals using microsatellite markers and plant chloroplastic single nucleotide polymorphisms. We found clear differentiation between fungal populations parasitizing S. nutans and S. italica plants. The population genetic structure of fungal strains parasitizing the S. nutans plant species complex mirrored the host plant genetic structure, suggesting that the pathogen was isolated in glacial refugia together with its host and/or that it has specialized on the plant genetic lineages. Using random forest approximate Bayesian computation (ABC‐RF), we found that the divergence history of the fungal lineages on S. nutans was congruent with that previously inferred for the host plant and probably occurred with ancient but no recent gene flow. Genome sequences confirmed the genetic structure and the absence of recent gene flow between fungal genetic lineages. Our analyses of individual host–pathogen pairs contribute to a better understanding of co‐evolutionary histories between hosts and pathogens in natural ecosystems, in which such studies remain scarce. 相似文献
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Pridacha Vladislava B. Sazonova Tatiana A. Novichonok Elena V. Semin Denis E. Tkachenko Yulia N. Pekkoev Alexey N. Timofeeva Vera V. Bakhmet Olga N. Olchev Alexander V. 《Plant and Soil》2021,466(1-2):317-336
Plant and Soil - Clear-cut logging currently is a key factor transforming forest communities in many boreal regions. The dynamics of biogeochemical processes taking place in clear-cuts makes them a... 相似文献
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Shahid N. Khan John D. Persons Michel Guerrero Tatiana V. Ilina Masayuki Oda Rieko Ishima 《Protein science : a publication of the Protein Society》2021,30(3):571
A clinically‐relevant, drug‐resistant mutant of HIV‐1 protease (PR), termed Flap+(I54V) and containing L10I, G48V, I54V and V82A mutations, is known to produce significant changes in the entropy and enthalpy balance of drug‐PR interactions, compared to wild‐type PR. A similar mutant, Flap+(I54A), which evolves from Flap+(I54V) and contains the single change at residue 54 relative to Flap+(I54V), does not. Yet, how Flap+(I54A) behaves in solution is not known. To understand the molecular basis of V54A evolution, we compared nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, isothermal titration calorimetry, and enzymatic assay data from four PR proteins: PR (pWT), Flap+(I54V), Flap+(I54A), and Flap+(I54), a control mutant that contains only L10I, G48V and V82A mutations. Our data consistently show that selection to the smaller side chain at residue 54, not only decreases inhibitor affinity, but also restores the catalytic activity. 相似文献
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Goncharov Alexey I. Levina Inna S. Shliapina Viktoriia L. Morozov Ivan A. Rubtsov Petr M. Zavarzin Igor V. Smirnova Olga V. Shchelkunova Tatiana A. 《Biochemistry. Biokhimii?a》2021,86(11):1446-1460
Biochemistry (Moscow) - Progesterone and its synthetic analogues act on cells through different types of receptors, affecting proliferation and apoptosis. These compounds exert their effect through... 相似文献
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Sukhorukov Vladimir S. Mudzhiri Natalia M. Voronkova Anastasia S. Baranich Tatiana I. Glinkina Valeria V. Illarioshkin Sergey N. 《Biochemistry. Biokhimii?a》2021,86(6):667-679
Biochemistry (Moscow) - Alzheimer’s disease is the most common age-related neurodegenerative disease. Understanding of its etiology and pathogenesis is constantly expanding. Thus, the... 相似文献
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