Alzheimer's disease Flashcards
True or False
The central dogma can have modifications in DNA, mRNA, or Protein that can affect the Transcription or Translation rates.
True
Match the following terms
(pre-mRNA / introns / exons / RNA splicing / mature RNA )
_______ RNA is transcribed from DNA initially.
_____ Section that remain in RNA
_____ Section that are removed in RNA
______ The process of removal of sections in RNA
________ Final Product of RNA
pre-mRNA
Exons
Introns
RNA splicing
Mature RNA
True or False
Multiple exons allow for the possibility of alternative splicing (the inclusion of different exons in mature mRNA) that results in different protein isoforms (variants).
True
Proteins can be altered after their biosynthesis through ________________
What are the two main categories of these PTMs?
Post-translational modifications
Reversible and irreversible
What are the common reversible and irreversible modifications that a protein can undergo?
Phosphorylation and dephosphorylation are common reversible modifications
Protein cleavage is a common irreversible modification
(a mechanism that quickly activate an enzyme)
True or False
Protein function is independent of proteins bring in the right place.
False
Protein function is dependent on proteins being in the right place. (Protein targeting)
Many of the common organelles with cells are involved in protein targeting.
The length of axons poses a challenge for protein targeting in neurons. Proteins are synthesized in cell bodies, so how do they transport at great distances along the axon?
Transport along axons is mediated by microtubules.
Molecular motors made out of protein kinesin allow anterograde transport (forward movement)
” “ those made out of protein dynein allow retrograde transport (backward movement)
True or False
Protein-mediated toxicity leads to cell death in both Huntington’s disease and Parkinson’s disease.
This reinforces the importance of understanding proteostasis (homeostatic regulation of protein synthesis, folding, modification, targeting, and degradation) for neurodegenerative disorder.
True
What are the first signs and symptoms of Alzheimer’s disease?
Mild cognitive impairment (MCI)
(noticeable cognitive decline beyond expectations from normal aging while individuals have preserved activities of daily living)
What does mild cognitive impairment often lead to?
Dementia
(impairment in thinking and memory)
True or False
Alzheimer’s can occur as familial or spordaic. Most cases are sporadic.
True
What are the two distinguishing features of neuropathology that are associated with Alzheimer’s disease?
Amyloid plaques (a.k.a. senile plaques)
Neurofibrillary (tau) tangles
________________ are extracellular aggregates of amyloid beta within brain gray matter, and they often aslo contain degenerative neural structures and glia.
________________ are intracellular aggregates of tay protein in cell bodies, dendrites, and axons.
Amyloid plaques
Neurofibrillary tangles
__________________ is a transmebrane protein with high abundance at the synapose. It is the precorusor of amyloid beta
Amyloid precursor protein (APP)
True or False
APP has multiple points of cleavage near AB.
an alpha site near the middle of AB
a beta site on the N-terminal side of AB
a gamma site on the C-terminal side
The production of AB depends on the order of cleavage
Cleavage is mediated by membrane-bound enzymes called secretases. Only occur when APP is bound to the membrane
All true
If alpha-secretase cuts the alpha site first, AB is (never/formed) and (do/do not) contain isoforms.
If beat-secretase cuts the beta site first hollowed by gamma-secretase on the gamma site, AB is (never/formed), and (do/do not) contains isoforms.
If gamma-secretase cuts either gamma -40 or -42 site, AB is (never/formed) and (do/do not) contain isoforms.
never ; do not
fomred ; do not
dormed ; do
AB-40 and AB-42(most toxic)
Choose the best option
(AB-40 / AB -42)
Tends to form protein aggregates
Oligomerization through beta-sheet bonding between multiple Ab-42 segements
AB-42
Point mutations of APP can alter the risk for Alzheimer’s and even cause Alzheimer’s with autosomal domain case and full penetrance.
Mutations can be considered in three categories, depending on proximity to alpha, beta, and gamma.
Mutations that increase the risk of Alzheimer’s near the ___ cleavage site tend to do so by increasing the chances of ___ cleavage.
Mutations that increase the risk of Alzheimer’s near the ___ cleavage site tend to do so by increasing the chances of ___ cleavage creating Ab-42 rather than AB-40.
Mutations that increase the risk of Alzheimer’s near the ___ cleavage site tend to do so by promoting AB oligomerization after AB is formed.
Beta
gamma ; gamma-42
alpha
True or False
Mutations in the secretases increase changes of gamma-42 cleavage creating AB-42 rather than AB-40.
True
________________- is a class of proteins involved in the transport and break down of molecules in the blood, especially fats and cholesterol. Common alleles are E2, E3, E4. Exerts large effects on Alzheimer’s risk, perhaps through a role in Ab clearance.
Apoliporotein E
True or False
Tau is a highly soluble protein involved in the stabilization of microtubules.
Abundant in neurons
Exists in multiple isoforms
True
In Alzheimer’s, tau becomes _____________________. This causes tau to dissociate from microtubules and form assemblies of paired helical filaments. Dissociation of tau from microtubules causes loss of microtubule stability and promotes breakdown. This leads to neuronal dysfunction.
hyperphosphorylated
What does the amyloid cascade hypothesis state?
That extracellular AB causes synaptic effects that alter intracellular phosphorylation of tau protein leading to microtubule breakdown.
True or False
Alzheimer’s causes exaggerated degeneration of the temporal cortex and hippocampus combined with severe loss of cholinergic neurons that supply input to both.
True
