Dementia Flashcards
What is a molecular chaperone?
Any protein that interacts with, stabilises or helps another protein to acquire its functionally active conformation, without being present in its final structure. Selectively binds to short stretches of hydrophobic amino acids.
What is a proteinopathy?
Accumulation of misfolded proteins resulting in aggregates, thereby gaining toxic activity or losing the normal function.
Problems with what proteins causes early onset familial AD?
Amyloid precursor protein (APP), Presenilin -1, and -2.
Problems with what protein lead to sporadic AD?
Apolipoprotein E E4 allele.
Abundance of what 2 abnormal structures are found in the brains of people with Alzheimer’s Disease?
1) Amyloid plaques in extracellular space.
2) Neurofibrillary tangles in cytoplasm.
Both are composed of misfolded proteins.
Where are presenilins found?
In gamma-secretases.
What are the main component of tangles?
Paired helical filaments. They consist of the microtubule associated protein tau.
How is tau involved in Alzheimer’s disease?
Abnormal hyperphosphorylation of tau leads to aggregates of it that form neurofibrill tangles. The abnormal tau phosphorylation that occurs in neurodegenerative conditions not only results in a toxic loss of function (e.g. decreased microtubule binding) but probably also a toxic gain of function (e.g. increased tau-tau interactions).
What are lewy bodies?
Alpha-synuclein aggregates.
What is proteostasis?
Maintenance of the cellular proteome. Dependent on efficient protein folding, detection of misfolding and degradation of defective proteins. Disrupted proteostasis, resulting from protein misfolding results in protein accumulation and insoluble aggregates.
What is Wilson’s disease?
Wilson disease is a rare autosomal recessive inherited disorder of copper metabolism that is characterized by excessive deposition of copper in the liver, brain, and other tissues.
