-
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
iNature Frontotemporal Lobar Degeneration (FTLD) is the third most common neurodegenerative disease after Alzheimer's and Parkinson's diseases
.
FTLD usually occurs in people 45-64 years old and manifests as behavioral changes or a gradual decline in language skills
.
The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions detected by TAR DNA-binding protein (TDP-43) immunoreactivity
.
On March 28, 2022, David S.
Eisenberg's team at UCLA (Cao Li from Shanghai Jiao Tong University and others are the first authors) published a paper in Nature online entitled "Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43 , which extracted amyloid fibrils from the brains of four patients, representing four of the five FTLD-TDP subclasses, and determined their characterization by cryo-electron microscopy (cryo-EM).
Near atomic resolution structure
.
Unexpectedly, all examined amyloid fibrils consisted of a 135-residue C-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously identified as FTLD-TDP genetic risk factors
.
In addition to TMEM106B fibrils, a large amount of non-fibrillar aggregates of TDP-43 was present, as revealed by immunogold labeling
.
Taken together, the observations of this study confirm that FTLD-TDP is an amyloid-related disease and suggest that amyloid in FTLD-TDP is associated with the protein TMEM106B, but not TDP-43
.
In addition, on March 28, 2022, the team of Sjors HW Scheres, University of Cambridge published a research paper titled "Age-dependent formation of TMEM106B amyloid filaments in human brains" online in Nature using cryo-electron cryo-microscopy (cryo-EM) Structural determination to show that residues 120-254 of lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brain
.
This study determined the cryo-EM structure of TMEM106B filaments from multiple brain regions of 22 individuals with abundant amyloid deposits, including sporadic and hereditary tauopathies, Aβ-amyloidopathies, synuclein disease and TDP-43 proteinopathy and from neurologically normal individuals with no or only minimal amyloid deposits
.
TMEM106B filaments were associated with the presence of a 29 kDa sarcosine-insoluble fragment and globular cytoplasmic inclusions, as detected by antibodies specific for the C-terminal region of TMEM106B
.
The identification of TMEM106B filaments in the brains of older, but not younger, neuronormal individuals suggests that they form in an age-dependent manner
.
Pathological deposition of amyloid is associated with more than 50 systemic and neurodegenerative diseases, including amyloid-beta and tau in Alzheimer's disease, alpha-synuclein and type II in Parkinson's disease hIAPP (or amylin) in diabetes
.
Recent advances in cryo-EM technology have allowed scientists to determine the near-atomic-resolution structure of amyloid fibrils extracted from patient tissue
.
Structural information from isolated fibrils provides insight into the molecular characteristics of disease and can guide the design of therapeutics aimed at preventing, delaying or reversing protein aggregation in amyloid diseases
.
About 81 out of 100,000 people between the ages of 45 and 64 have FTLD leading to Alzheimer's disease
.
FTLD is clinically manifested by impairments in social behavior and language abilities
.
The major subtype of FTLD is characterized by neuronal inclusions containing TDP-43, termed FTLD-TDP, and accounts for approximately 50% of all FTLD cases
.
Based on the morphology and neuroanatomical distribution of TDP-43 inclusions, FTLD-TDP is further divided into types A to E; each type is associated with different clinical symptoms
.
Cryo-EM structure of TMEM106B fibrils from FTLD-TDP donor 1 (figure from Nature) Although the defining neuropathological feature of FTLD-TDP is immunoreactivity to ubiquitinated, hyperphosphorylated TDP-43 deposits, Structural studies of amyloid fibrils in FTLD-TDP brains have not yet been performed
.
Here, the study extracted amyloid fibrils from four donors diagnosed with type A to D FTLD-TDP and determined the structure at near-atomic resolution by cryo-electron microscopy
.
Through atomic modeling, mass spectrometry, and western blotting, the study confirmed that these fibrils were formed by TMEM106B, a protein previously identified as a genetic risk factor for FTLD-TDP
.
In conclusion, this study uncovers the amyloidogenic properties of TMEM106B in FTLD-TDP and focuses attention on proteins not previously associated with amyloid disorders
.
Reference information: https:// https://
.
FTLD usually occurs in people 45-64 years old and manifests as behavioral changes or a gradual decline in language skills
.
The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions detected by TAR DNA-binding protein (TDP-43) immunoreactivity
.
On March 28, 2022, David S.
Eisenberg's team at UCLA (Cao Li from Shanghai Jiao Tong University and others are the first authors) published a paper in Nature online entitled "Amyloid fibrils in disease FTLD-TDP are composed of TMEM106B not TDP-43 , which extracted amyloid fibrils from the brains of four patients, representing four of the five FTLD-TDP subclasses, and determined their characterization by cryo-electron microscopy (cryo-EM).
Near atomic resolution structure
.
Unexpectedly, all examined amyloid fibrils consisted of a 135-residue C-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously identified as FTLD-TDP genetic risk factors
.
In addition to TMEM106B fibrils, a large amount of non-fibrillar aggregates of TDP-43 was present, as revealed by immunogold labeling
.
Taken together, the observations of this study confirm that FTLD-TDP is an amyloid-related disease and suggest that amyloid in FTLD-TDP is associated with the protein TMEM106B, but not TDP-43
.
In addition, on March 28, 2022, the team of Sjors HW Scheres, University of Cambridge published a research paper titled "Age-dependent formation of TMEM106B amyloid filaments in human brains" online in Nature using cryo-electron cryo-microscopy (cryo-EM) Structural determination to show that residues 120-254 of lysosomal type II transmembrane protein 106B (TMEM106B) also form amyloid filaments in human brain
.
This study determined the cryo-EM structure of TMEM106B filaments from multiple brain regions of 22 individuals with abundant amyloid deposits, including sporadic and hereditary tauopathies, Aβ-amyloidopathies, synuclein disease and TDP-43 proteinopathy and from neurologically normal individuals with no or only minimal amyloid deposits
.
TMEM106B filaments were associated with the presence of a 29 kDa sarcosine-insoluble fragment and globular cytoplasmic inclusions, as detected by antibodies specific for the C-terminal region of TMEM106B
.
The identification of TMEM106B filaments in the brains of older, but not younger, neuronormal individuals suggests that they form in an age-dependent manner
.
Pathological deposition of amyloid is associated with more than 50 systemic and neurodegenerative diseases, including amyloid-beta and tau in Alzheimer's disease, alpha-synuclein and type II in Parkinson's disease hIAPP (or amylin) in diabetes
.
Recent advances in cryo-EM technology have allowed scientists to determine the near-atomic-resolution structure of amyloid fibrils extracted from patient tissue
.
Structural information from isolated fibrils provides insight into the molecular characteristics of disease and can guide the design of therapeutics aimed at preventing, delaying or reversing protein aggregation in amyloid diseases
.
About 81 out of 100,000 people between the ages of 45 and 64 have FTLD leading to Alzheimer's disease
.
FTLD is clinically manifested by impairments in social behavior and language abilities
.
The major subtype of FTLD is characterized by neuronal inclusions containing TDP-43, termed FTLD-TDP, and accounts for approximately 50% of all FTLD cases
.
Based on the morphology and neuroanatomical distribution of TDP-43 inclusions, FTLD-TDP is further divided into types A to E; each type is associated with different clinical symptoms
.
Cryo-EM structure of TMEM106B fibrils from FTLD-TDP donor 1 (figure from Nature) Although the defining neuropathological feature of FTLD-TDP is immunoreactivity to ubiquitinated, hyperphosphorylated TDP-43 deposits, Structural studies of amyloid fibrils in FTLD-TDP brains have not yet been performed
.
Here, the study extracted amyloid fibrils from four donors diagnosed with type A to D FTLD-TDP and determined the structure at near-atomic resolution by cryo-electron microscopy
.
Through atomic modeling, mass spectrometry, and western blotting, the study confirmed that these fibrils were formed by TMEM106B, a protein previously identified as a genetic risk factor for FTLD-TDP
.
In conclusion, this study uncovers the amyloidogenic properties of TMEM106B in FTLD-TDP and focuses attention on proteins not previously associated with amyloid disorders
.
Reference information: https:// https://
