Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

ATU 1 > Neuro - general > Flashcards

Neuro - general Flashcards

1
Q

Symptoms of PD?

A 
Akinetic-rigid
Bradykinesia
Loss of movement
Increased muscle tone
Resting tremor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Is PD predominantly inherited or non-inherited?

A

Non-inherited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Where are dopamine neurons lost on PD?

A

SN - 50% lost for symptoms and 80% at autopsy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where are cells lost in PD?

A 
Substantia nigra
Locus ceruleus
Dorsal motor of the vagus
Raphe nuclei
Brain stem structures
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe lewy bodies

A 
Spherical
Intracellular
Eosinophillic core
Pale halo
Filamentous and granular material
Neurofilament proteins, Ubiquitin and Lipids
Major alpha-syn
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the PARK genes?

A

15 causing genes

PARK 1/4, 2, 5 and 8 all found to be involved in membrane trafficking and UPS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe alpha-syn

A

PARK1/4
140aa protein
found at presynaptic terminals
Thought to be involved in synaptic plasticity, membrane trafficking and vesicle sorting
Mutations can cause aggregation (A53T, A30P, E46T and WTx3 Iowan)
Gene replication can cause PD
Aggregable (also found in AD plaques)
Upon binding to membrane it forms an amp alpha helix
Central hydrophobic region self-associates and aggregates (region not shared with beta-syn)
C-terminal acidic tail inhibits aggregation hence why truncation can lead to aggregation
A53T - 50% longer half-life than the WT shows it is not degraded as efficiently
Contains a KFERQ-like motif - think CMA dominant degradation pathway with LAMP2A/Hsc70 but cannot be translocated into the lumen which enhances aggregation and blocks other protein degradation
PD neurons have decreased levels of Cathepsin D, LAMP-2A and Hsc70
Macroautophagy which can degrade aggregates is also inhibited - rapamycin which inhibits mTOR stimulates macroautophagy which promotes alpha-syn aggregation clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe LRRK2

A

PARK 8
Leucine-rich repeat kinase
Mutated forms found in PD - G2019S
Member of the ROCO family contains a MAPKKK (kinase effector domain) and a ROC-GTP domain (GTP binding regulation domain)
G2019S found in the MAPKKK domain
In rats vectors containing LRRK2 were injected in one side of the brain - KO of LRRK2 cause neurite outgrowth and branching whereas G2019S caused no neurite outgrowth or branching. Suggests that the mutations cause P of its targets without regulation one of its targets is Tau
Found in the striatum
See a reduction of LRRK2 in PD dopamine neurones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe Parkin

A

PARK 2
Encodes a E3 Ub-ligase and is thought to be protective against PD
Can bind Ub and alpha-syn and target it for degradation
Mutations cause loss of function and therefore PD by getting alpha-syn build up
Overexpressed Parkin and alpha-syn and looked at dopamine neurones by staining for tyrosine hydroxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe UCHL1

A

PARK 5
De-Ub enzyme - removes Ub from the C-terminal bond
Mutations are loss of function and cause PD/PD-like syndromes
Present in Lewy bodies
Important for keeping the Ub pool in the cell - can inhibit other protein degradation by not restoring the Ub pool

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe PINK1

A

Serine/threonine protein kinase
N-terminal mitochondrial localization signal
Protects the cell against apoptosis induced by proteasome inhibition
Loss of function causes PD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe DJ-1

A

Redox sensitive molecular chaperone
Loss of function leads to PD through sensitivity to oxidative stress
L166P mutation promotes cytoplasm –> mitochondria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Treatments for PD - autologous graft

A

Take adrenal chromaffin cells from the same patient and transplant into the striatum and they release dopamine
No immunosuppresion needed
Stopped as saw adverse psychiatric effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Treatments for PD - fetal transplant

A

Take SN from aborted fetuses and transplant into the caudate nucleus
Worked well but side effects of Bradykinesias
Ethical issues - need 6-8 fetuses as 90% of cells die, needed immunosuppression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Treatments for PD - stem cells

A

Take stem cells either from a different organism or the same one and induce to differentiate into DA neurons
Transplants in aminal models but number of problems - hard to get the stem to stop dividing so DA tumor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Treatments for PD - Deep brain stimulation

A 
Place electrodes into the STN
Pacemaker fitted so patient can control
Mimic a lesion to reverse the signals
Works quickly
Tends to be done in younger patients as better for op
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Treatments for PD - Growth factors and gene therapy

A

Gene therapy:
Lentivirus and adenovirus vectors contain a gene e.g. parkin or tyrosine hydroxylate
Delivery to specific area can be problematic and crossing BBB - conbine with transplant - Varying sucess in animals

Growth factors:
Infuse with a catheter as cannot cross BBB
Close to the striatum
GDNF - dissapointing
Neurturin
GDF5 - preclincal development
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

When was AD first discovered?

A

1907 by Alois Alzheimer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the most common form of dementia

A

AD of 80% of cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Symptoms of AD?

A

Changes in personality, memory loss, confusion, hallucinations and many more

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Who donated her brain to AD research and what did he find?

A

Auguste Deter

Found plaques and tangles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the first region affected in AD? then where?

A

Hippocampus then spreads to the frontal lobes/back of the brain then throughout the cortex regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the average number of years after diagnosis for AD?

A

8 years but varies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Draw the amyloid cascade theory

A

See diagram

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Draw A-beta production
See diagram
26
What are the proteins which make up gamma secretase?
PS1/2, Pen2, Aph1a/b and Nicostatin
27
How many different isoforms of gamma secretase?
4 vary in PS1/2 and aph1a/b
28
What is the ratio of sporadic AD to familial
90% and 10% Early onset/familial before 65 years Pathologies are similar​ so can inform us
29
What are the genes which cause early onset/familial AD?
Mutations it APP, PS1 and PS2
30
What does the Swedish mutation cause in APP?
Increases beta-secretase cleavage
31
What does the Flemish mutation cause in APP?
Changes the A-beta structure which causes it to aggregate quicker
32
What do the Florida and Australian mutations cause in APP?
more 42 production which is less soluble and aggregates quicker therefore more toxic
33
Mutations in PS1/2 cause?
More 42 production - cause APP to move more inside the cleavage site causes change in 42 vs 40 ratio
34
Down syndrome and AD?
Trisomy 21 Where APP is located so more A-beta over their life-time Early onset at late 30s
35
Protection mutation in AD?
A673T People over 85+ without AD 20% less A-beta production Protects against cognitive decline
36
Neurotoxic form of a-beta?
Soluble oligomers/pores Can move around the body and bind to membranes in the synapses altering comminucations --> toxic and death Oligomers induce oxidative damage and hyper-P of tau which forms NFTs
37
What are the pathways which degrade A-beta?
IDE, RAGE, A2M and LRP
38
Risk factors in sproadiac AD?
``` ApoE PICALM CLU CR1 Found during a huge meta-analysis project in 2013 ```
39
ApoE?
Apolipoprotein of the HDL complex in the brain Can bind A-beta Different isoforms of ApoE generally thought to reduce A-beta however the E4 isoform increases Ab depoistition whereas E2/3 decrease it
40
What are the symptomatic relief for AD?
Neurotransmission is distrupted so NMDA anatagonist and chloinesterase inhibitors
41
What are the three areas for potential therapies in AD?
1) A-beta production - alpha increase, beta and gamma decrease and alter APP trafficking 2) . A-beta degrdation - activation of degradation enzymes e.g. ICE, ACE, ECE-1 and immuno therapy 3) . A-beta aggregate formation - prevent toxic effects and allow easier degrdation
42
What is the function of Tau?
MT associated protein Binds and stabilizes MTs by promoting polymerisation aiding neuronal axonal transport and structure When P at are range of serine/threonine residues prevents binding to MT therefore inhibits transport down the axon
43
What does hyper-P of Tau do?
Impairs normal function and also forms paired-helical filaments which are the building blocks of neurofibril tangles which are insoluble amyloidogenic aggregates in neuronal cell bodies/processes and glia leading to neuronal dysfunction/death or a marker of neuronal death
44
What are the genetic factors associated with Tau dysfunction?
Tau mutations, APP/PS1/2 mutations or other Perturbation of 4R/3R ratio, loss of Tau function and gain of toxic function which leads to Tau dysfunction, aggregation and MT loss then impaired transport and neurodegeneration
45
What are the 3 types of Tau immunopositive inclusions?
Pick inclusion bodies which are tau-positive, spherical, cytoplasmic inclusions composed of straight filaments NFTs/neuritic threads in the gray matter of the frontal cortex Perinuclear inclusions of the frontal cortex
46
Names 3 tau-positive inclusion diseases
AD FTDP17 Pik's disease Dementia pugilistica
47
Which diseases is tau a secondary event in?
AD PD - alpha-syn colocalizes with tau in neurons carrying the A53T mutation Huntington's - inclusion colocalize with tau in neurons
48
How can we image Tau and A-beta?
PET scans with PiB for A-beta amyloid and PBB3 for Tau | Possibilty for biomarkers
49
Known tau mutations leading to neurodegeneration
Mutations impairing tau protein function - G272V Mutations promoting tau aggregation - G272V Mutations altering exon 10 splicing - D280K
50
Is there different isoforms of Tau?
Yes - caused by different splice variants 4 repeat forms of Tau lead to increases aggregation Have different biological roles within the brain Can have different post-translational modifications such as P
51
Clinical features of FTD
Clinical group of neurodegenerative syndromes Mean age 55-65 Male>Female Frontal lobe symptoms e.g. personality changes, loss of socially acceptable behaviour, language dysfunction, movement disorder Internation research criteria for diagnosing
52
What percentage of dementia is FTD?
10-15% in the US | More common than AD below 60
53
What are the 3 neuro-circuit effects in AD?
Dorsolaterol prefrontal cortex Anterior cingulate cortex Orbitofrontal cortex Give different symptoms - very hard or doctors to recongise whats happening
54
Draw the subtypes of FTD
See diagram
55
FTD inheritance? Which chromosomes are effected?
Autosomal dominant pattern of inheritance - 10% have a single gene mutation Chromosomes 3p, 9, 9p and 17q
56
What are the most prevelant genes in FTD? and which others?
Progranulin and tau located on 17q21 TDP43 FUS C9ORF72
57
The autosomal dominant form of FTD?
FTDP-17 linked to chromosome 17q21
58
What are the 2 main hallmarks of clinical FTD?
FTLD 1) . histopathologic diagonosed with neuronal and gliosis, spongiosis and ballooned neurons 2) . Abnormal protein inclusions: tauopathies (Tau+), TDP-43 (Tau= but TDP43 and Ub+) or FUS (Tau neg but FUS and Ub+)
59
What are the functions of TDP-43?
``` TAR DNA binding protein Transcription regulation Exon splicing mRNA stablisation Neuronal activity-response factor ```
60
Is TDP-43 inclusions amyloidogenic?
No
61
What are the potential mechanisms of TDP-43 neurodegeneration
Aggregation and sequestration of TDP-43 leading to either dystrophic neurites, cytoplasmic inclusions or intranuclear inclusions All loss of function or can have toxic gain of function
62
Current drugs for FTD?
Antipsychotics (block dopamine), antidepressants and NMDA receptor antagonists
63
Targets in FTD for drugs?
Tau kinases inhibit the P Inhibit the tau filrillizstion MT stablising agents TDP-43 inhibitting aggregation

ATU 1 (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions