Tauopathies Flashcards
Define tau
microtubules associated protein that promotes tubulin assembly into microtubules
Microtubules are the __ for __ __
tracks
axonal transport
When __ are disrupted, there is __
microtubules, neurodegeneration
Normal tau uses __ to make P-tau
P-tau uses __ to make normal tau
kinases
phosphetases
List five tauopathies
alzheimer disease
postencephalitic parkinsonism
ALS/ Parkinsonism dementia complex (PDC) of Gua,
Progressive subnuclear palsy (PSP)
corticobasal degeneration (CBD)
Pick’s disease
Frontotemporal dementia (FTD)
Myotonic dystrophy
niemann-Pick Type C (NPC) disease
Dementia pugillistica
chronic traumatic encephalophay (CTE)
What is the manifestation of CTE
hypophosphorylated tau accumulates in the absence of amyloid plaques
Define alzheimer’s and describe the clinical symptoms
a progressive, degenerative disease that attacks the brain and results in dementia – impaired memory, thinking and behavior
Clinical symptoms - the disease progresses slowly from mild forgetfulness to confusion and dementia
There are six isoforms in the adult human brain of __ __ __ __, all products of __ -_ from a single gene
microtubule associated protein tau
alternate splicing
what is the function of microtubule associated protein tau?
promotes assembly and maintains the structure of microtubules by co-assembling with tubulin
What are the three types of tau found in an AD brain?
abnormally phosphorylated and polymerized into PHF
normally phosphorylated
abnormally hyperphosphorylated (AD P-Tau) and unpolymerized
What are the three steps of tubulin assembly into microtubules
nucleation, elongation, steady state
Hyperphosphorylated tau __ tau-promoted __ assembly
inhibited
microtubule
AD P-tau binds normal tua in a __ __ fasion
non-saturable
AD P-tau induces __ tau to acquire __ conformation
normal
pathological
Self-assembly of AD P-Tau is dependent on __
phosphorylation
T/F: Soluble and not PHF-tau is able to disrupt microtubules
true
Describe the four common characteristics of hyperphosphorylated tau from Alzheimer brain cytosol (AD P-tau)
Inhibits the microtubule assembly
disrupts the pre-assembled microtubules
self-polymerizes into PHF/SF
dephosphorylation eliminates both the microtubule assembly inhibitory activity and self-polymerizes into filaments of AD P-tau
Hyperphosphorylation converts __ __ into an AD P-tau like molecule
recombinant tau
FTDP-17 mutations induce a __ change to __, making it a more __ substrate for __
Conformational
tau
favorable
phosphorylation
The mutated taus on phosphorylation sequester normal __ and __ __ into __
tau
self-aggregate
filaments