-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Responsible Editor | The pathological amyloid fibril aggregation formed by Zyme α-Syn through liquid-solid phase transformation is the main pathological sign of Parkinson's disease (PD).
The formation of α-Syn pathological fibers and their spread between cells are closely related to the occurrence and development of PD.
Multiple autosomal dominant mutation sites of α-syn have been discovered in familial inherited PD.
Familial PD caused by different point mutations of α-Syn usually has the characteristics of early onset and rapid development of the disease.
The previous work of Liu Cong’s research group from the Center for Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences found that mutations at different sites (such as E46K, A53T, etc.
) and phosphorylation modifications can induce the formation of α-syn which is different from wild-type (wild-type).
, WT) pathological fibers (PNAS | Liu Cong/Li Yanmei collaborate to reveal the molecular mechanism of post-translational modification regulating the liquid-solid phase transformation and aggregation of Parkinson’s disease-causing protein α-syn), in order to understand the structural polymorphism of protein fibers And the high degree of heterogeneity of related diseases provides molecular mechanisms.
However, how are α-syn pathological fibers with different structures selectively induced? Do the mutant and wild-type α-syn co-existing in heterozygotes affect each other in fiber formation? How to explain the pathological characteristics of familial PD early onset? These are important scientific issues that have not been resolved in this field.
Recently, Liu Cong’s research group cooperated with the same unit He Kaiwen research group to publish a new research result online on PNAS on May 11, 2021, titled Wild-type α-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding.
The authors found that E46K mutant fibers have stronger pathological toxicity than WT fibers, and can induce endogenous α-syn in the mouse brain to form pathological fibers with a faster transmission speed, leading to early-onset motor deficits in mice.
More importantly, E46K fibers can induce WT α-syn to form E46K fiber structures through cross-seeding, indicating that heterozygous E46K mutations can cause pathological changes similar to homozygous mutations.
Related work provides a new perspective for understanding the selectivity of α-syn fiber structure and the pathogenesis of familial PD.
In this work, the researchers first constructed a PD mouse model in which α-syn pathological fibers were injected through the brain stereotactically, and found that E46K fibers can trigger early-onset motor deficits in mice, and cause a large amount of endogenous in the brains of mice.
Pathological aggregates of α-syn.
Compared with WT α-syn fibers, E46K fibers induce endogenous α-syn to produce smaller fibers and are more inclined to distribute in neuronal synapses rather than cell bodies, showing stronger fluidity and cell-to-cell transmission.
ability.
More interestingly, the researchers found that using E46K fibers as seeds in vitro can effectively induce WT α-syn to form the structure of E46K fibers.
Furthermore, the researchers directly extracted the endogenously induced aggregation of α-syn fibers from the brains of PD mice injected with E46K fibers, and expanded them in vitro.
Using atomic force microscopy, it was found that E46K induced fibers from endogenous WT α-syn in the mouse brain faithfully copied the structure of E46K fibers.
Therefore, E46K fiber can transmit its pathological conformation to WT α-syn through cross-seeding, and jointly cause the early onset of PD.
At present, most of the familial mutations of α-syn, including E46K, are heterozygous mutations, that is, WT and mutant α-syn coexist in patients.
Therefore, the findings of this study have changed the understanding of the pathogenesis of familial PD to a certain extent.
Original link: https://doi.
org/10.
1073/pnas.
2012435118 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights.
Research.
The formation of α-Syn pathological fibers and their spread between cells are closely related to the occurrence and development of PD.
Multiple autosomal dominant mutation sites of α-syn have been discovered in familial inherited PD.
Familial PD caused by different point mutations of α-Syn usually has the characteristics of early onset and rapid development of the disease.
The previous work of Liu Cong’s research group from the Center for Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences found that mutations at different sites (such as E46K, A53T, etc.
) and phosphorylation modifications can induce the formation of α-syn which is different from wild-type (wild-type).
, WT) pathological fibers (PNAS | Liu Cong/Li Yanmei collaborate to reveal the molecular mechanism of post-translational modification regulating the liquid-solid phase transformation and aggregation of Parkinson’s disease-causing protein α-syn), in order to understand the structural polymorphism of protein fibers And the high degree of heterogeneity of related diseases provides molecular mechanisms.
However, how are α-syn pathological fibers with different structures selectively induced? Do the mutant and wild-type α-syn co-existing in heterozygotes affect each other in fiber formation? How to explain the pathological characteristics of familial PD early onset? These are important scientific issues that have not been resolved in this field.
Recently, Liu Cong’s research group cooperated with the same unit He Kaiwen research group to publish a new research result online on PNAS on May 11, 2021, titled Wild-type α-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding.
The authors found that E46K mutant fibers have stronger pathological toxicity than WT fibers, and can induce endogenous α-syn in the mouse brain to form pathological fibers with a faster transmission speed, leading to early-onset motor deficits in mice.
More importantly, E46K fibers can induce WT α-syn to form E46K fiber structures through cross-seeding, indicating that heterozygous E46K mutations can cause pathological changes similar to homozygous mutations.
Related work provides a new perspective for understanding the selectivity of α-syn fiber structure and the pathogenesis of familial PD.
In this work, the researchers first constructed a PD mouse model in which α-syn pathological fibers were injected through the brain stereotactically, and found that E46K fibers can trigger early-onset motor deficits in mice, and cause a large amount of endogenous in the brains of mice.
Pathological aggregates of α-syn.
Compared with WT α-syn fibers, E46K fibers induce endogenous α-syn to produce smaller fibers and are more inclined to distribute in neuronal synapses rather than cell bodies, showing stronger fluidity and cell-to-cell transmission.
ability.
More interestingly, the researchers found that using E46K fibers as seeds in vitro can effectively induce WT α-syn to form the structure of E46K fibers.
Furthermore, the researchers directly extracted the endogenously induced aggregation of α-syn fibers from the brains of PD mice injected with E46K fibers, and expanded them in vitro.
Using atomic force microscopy, it was found that E46K induced fibers from endogenous WT α-syn in the mouse brain faithfully copied the structure of E46K fibers.
Therefore, E46K fiber can transmit its pathological conformation to WT α-syn through cross-seeding, and jointly cause the early onset of PD.
At present, most of the familial mutations of α-syn, including E46K, are heterozygous mutations, that is, WT and mutant α-syn coexist in patients.
Therefore, the findings of this study have changed the understanding of the pathogenesis of familial PD to a certain extent.
Original link: https://doi.
org/10.
1073/pnas.
2012435118 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights.
Research.
