Podcast
Questions and Answers
In Pick's disease, the Tau amyloid filaments are characterized as paired helical filaments.
In Pick's disease, the Tau amyloid filaments are characterized as paired helical filaments.
False
The amyloid fibril structure is templated by SOD1 fibril structure.
The amyloid fibril structure is templated by SOD1 fibril structure.
True
The on-target protein folding landscape is related to aggregation of proteins.
The on-target protein folding landscape is related to aggregation of proteins.
False
Corticobasal degeneration is characterized by Type II filament.
Corticobasal degeneration is characterized by Type II filament.
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Positron emission tomography (PET) imaging is used to detect amyloid within the brain without injection of a radiotracer.
Positron emission tomography (PET) imaging is used to detect amyloid within the brain without injection of a radiotracer.
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Amyloid precursor protein is not mutated in disease.
Amyloid precursor protein is not mutated in disease.
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The protein responsible for frontotemporal dementia is 𝛂-synuclein.
The protein responsible for frontotemporal dementia is 𝛂-synuclein.
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The protein TDP-43 is associated with Alzheimer’s disease.
The protein TDP-43 is associated with Alzheimer’s disease.
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The protein involved in light chain amyloidosis is Immunoglobin light chain.
The protein involved in light chain amyloidosis is Immunoglobin light chain.
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The protein responsible for Hereditary cerebral hemorrhage with amyloidosis, Icelandic type is Lysozyme.
The protein responsible for Hereditary cerebral hemorrhage with amyloidosis, Icelandic type is Lysozyme.
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The protein Amyloid in non-neurodegenerative diseases is associated with Familial amyloid cardiomyopathy.
The protein Amyloid in non-neurodegenerative diseases is associated with Familial amyloid cardiomyopathy.
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The protein involved in Heavy chain amyloidosis is Immunoglobin heavy chain.
The protein involved in Heavy chain amyloidosis is Immunoglobin heavy chain.
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In killifish, proteins with high hydropathy are found in the brain aggregates.
In killifish, proteins with high hydropathy are found in the brain aggregates.
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Up to 20% of the proteome is translated and immediately degraded.
Up to 20% of the proteome is translated and immediately degraded.
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In killifish, muscle deterioration is accompanied by neurodegeneration.
In killifish, muscle deterioration is accompanied by neurodegeneration.
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Protein biophysical properties are not a predictor of aggregation location.
Protein biophysical properties are not a predictor of aggregation location.
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Cognitive impairment is not a result of killifish aging.
Cognitive impairment is not a result of killifish aging.
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Reduction in protein quality control creates functional proteins that can be folded and degraded.
Reduction in protein quality control creates functional proteins that can be folded and degraded.
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Study Notes
Tau Amyloid in Different Diseases
- Pick's disease is associated with narrow Pick filaments (6GX5) (Falcon et al, 2018)
- Alzheimer's disease (AD) is associated with paired helical filaments (5O3L) (Fitzpatrick et al, 2017)
- Corticobasal degeneration is associated with Type I filaments (6TJO) (Zhang et al, 2020)
- Chronic traumatic encephalopathy is associated with Type I filaments (6NWP) (Falcon et al, 2019)
Multiple Amyloid Conformers
- Multiple amyloid conformers can exist in the same individual, as seen in AD brain (Fitzpatrick et al, 2017)
Positron Emission Tomography (PET) Imaging
- PET imaging allows for the detection of amyloid within the brain following injection of a radiotracer (Chapleau et al, 2022)
Protein Misfolding and Conversion to Amyloid
- The process of protein misfolding and conversion to amyloid involves an intermediate state, small oligomers, and amyloid fibers growing by addition of monomers at their termini (Wang et al, 2022)
Aggregation and Protein Folding
- Aggregation is an off-pathway folding process (Adamcik, 2018)
- On-target and off-target protein folding landscapes exist (Adamcik, 2018)
Amyloid-Forming Proteins in Disease
- Amyloid-forming proteins are sometimes mutated in disease, but most frequently they are wild-type (Goate et al, 1991; Spillantini et al, 1998; Polymeropoulos et al, 1997; Rosen et al, 1993; Kabashi et al, 2008)
Amyloid in Non-Neurodegenerative Diseases
- Light chain amyloidosis (AL) is associated with immunoglobin light chain
- Heavy chain amyloidosis (HL) is associated with immunoglobin heavy chain
- AA amyloidosis is associated with serum amyloid A protein
- Various other diseases, including familial amyloid cardiomyopathy, dialysis-related amyloidosis, and hereditary non-neuropathic systemic amyloidosis, are associated with different amyloid-forming proteins
The HSP90 Chaperone Machinery
- The HSP90 chaperone machinery is involved in the proteostasis network and its decline in aging (Schopf et al, 2017; Hip et al, 2019)
Protein Aggregation in Killifish
- As killifish age, they undergo muscle deterioration, fertility decline, cognitive impairment, and neurodegeneration
- Protein aggregation is widespread, tissue-specific, and protein-specific in aging killifish (Chen et al, 2022)
Protein Quality Control
- Up to 30% of the proteome is translated and immediately degraded (Schubert et al, 2000)
- 85% of the proteome interacts with folding chaperones (To et al, 2022)
- Reduction in protein quality control creates "zombie proteins" that cannot be folded or degraded
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Description
This quiz covers the different types of amyloid filaments found in various neurodegenerative diseases, including Alzheimer's disease, Pick's disease, and corticobasal degeneration. It also explores the different conformers of amyloid filaments in the same individual.
