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Neurobiology of Adult Brain Disorders > Tauopathies > Flashcards

Tauopathies Flashcards

1
Q

Define tau

A

microtubules associated protein that promotes tubulin assembly into microtubules

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2
Q

Microtubules are the __ for __ __

A

tracks
axonal transport

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3
Q

When __ are disrupted, there is __

A

microtubules, neurodegeneration

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4
Q

Normal tau uses __ to make P-tau
P-tau uses __ to make normal tau

A

kinases
phosphetases

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5
Q

List five tauopathies

A

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)

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6
Q

What is the manifestation of CTE

A

hypophosphorylated tau accumulates in the absence of amyloid plaques

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7
Q

Define alzheimer’s and describe the clinical symptoms

A

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

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8
Q

There are six isoforms in the adult human brain of __ __ __ __, all products of __ -_ from a single gene

A

microtubule associated protein tau
alternate splicing

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9
Q

what is the function of microtubule associated protein tau?

A

promotes assembly and maintains the structure of microtubules by co-assembling with tubulin

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10
Q

What are the three types of tau found in an AD brain?

A

abnormally phosphorylated and polymerized into PHF

normally phosphorylated

abnormally hyperphosphorylated (AD P-Tau) and unpolymerized

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11
Q

What are the three steps of tubulin assembly into microtubules

A

nucleation, elongation, steady state

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12
Q

Hyperphosphorylated tau __ tau-promoted __ assembly

A

inhibited
microtubule

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13
Q

AD P-tau binds normal tua in a __ __ fasion

A

non-saturable

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14
Q

AD P-tau induces __ tau to acquire __ conformation

A

normal
pathological

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15
Q

Self-assembly of AD P-Tau is dependent on __

A

phosphorylation

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16
Q

T/F: Soluble and not PHF-tau is able to disrupt microtubules

A

true

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17
Q

Describe the four common characteristics of hyperphosphorylated tau from Alzheimer brain cytosol (AD P-tau)

A

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

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18
Q

Hyperphosphorylation converts __ __ into an AD P-tau like molecule

A

recombinant tau

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19
Q

FTDP-17 mutations induce a __ change to __, making it a more __ substrate for __

A

Conformational
tau
favorable
phosphorylation

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20
Q

The mutated taus on phosphorylation sequester normal __ and __ __ into __

A

tau
self-aggregate
filaments

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21
Q

__ levels of phosphorylation are required for self-assembly of mutated taus than __ __ taus

A

lower; wild type

22
Q

FTDP-17 mutations cause the disease probably by making __ and preferred substrate for __

A

tau; phosphorlyation

23
Q

T/F: Pseudophosphorylation at Ser 199, Ser 396 does not significantly alter tau’s ability to bind to microtubules

24
Q

Tau pseduophosphorylated at Ser262 binds __ to microtubules

25
TauR406W with Tau212 mutated to __ seems to aggregate without _- but attached to __ in permeabilized CHO cells
Glu tubulin microtubules
26
T/F: Pseudophosphorylation at single site makes tau and AD P-tau-like molecule
False; does not make AD P-tau
27
3E-tau expression induces __ in CHO cells
apoptosis
28
Pseudophosphorylated tau at Thr212, 231 and Ser 262 (3E-Tau) induces __ __ in CHO cells
capase activation
29
T/F: Normal tau binds to tubulin in CHO cells
true
30
Expression of __ disrupts the microtubule network in CHO cells
PH-tau
31
__ are released from PH-tau transfected CHO cells
vesicles
32
Describe the charactersticis of microtubules with PH-tau infection
PH tau enters the nucleus PH-tau expressing cells have membrane blebbing Intracellular degeneration and protein aggregation, vacuole formation
33
Tau has a __ that becomes functional upon __
NLS, hyperphosphorylation
34
PH-Tau translocates into the __ via __ binding
nucleus; importin
35
Translocation of PH-tau into the nucleus promotes __
cell death
36
Tau nuclear translocation disrupts the ___ __
nucleo-cytoplasmatic transport
37
TDP-43 changes its __ localization when __ is expressed in the cells
nuclear; PH-Tau
38
What are two models used to study Tau pathological effects?
transgenic drosophila inducible transgenic mice model
39
T/F: neuronal loss is present in greater quantities in PH-Tau mice
true
40
PH-Tau induces synaptic __ and __ disruption
dysfunction; axonal
41
PH-tau expressed basal levels in the presence of __ and the expression can be increased by the removal of __ from the diet
doxycycline; doxycycline
42
Basal PH-tau expression leads to early __ deficits; PH-Tau was detected as __ tau
behavioral; oligomeric
43
Induced expression of PH-Tau resulted in sarkosyl __ tau and __ tau, extensive __ loss and __ activation
insoluble; truncated; neuronal; astrocytes
44
Alzheimer's disease has been associated with a disruption of __ signaling cascade in __, and to __ resistance. T2DM correlates with AD
insulin; neurons; insulin resistance
45
Describe characteristics of PH-Tau-TG mice
have higher elevated levels of expression of activated insulin receptor and glucose transporters have higher levels of fasting glucose in plasma show electrophysiological signs of brain insulin resistance
46
What are two effects of PH-Tau injections in vivo?
change in cell morphology neurodegeneration
47
PH-Tau injection leads to __ decline __ months post-injection
cognitive; six
48
Abnormal __ of tau is an early step in the process of __ degeneration
hyperphosphorylation; neurofibrillary
49
The combination of phosphorylation at __, __, and __, __ in the same tau molecule can trigger toxicity in vitro and in vivo
Thr 212, 231 Ser 199, 262
50
What does the new inducible mouse model recaptiulate?
oligomeric tau truncated tau early cognitive impairment neuronal loss and astrocytes activation
51
Blocking __ receptors with __ resulted in inhibition of tau uptake
muscarinic; atropine
52

Neurobiology of Adult Brain Disorders (10 decks)

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