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Flashcards in Exam #2 Deck (73)
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1

What does SNR stand for?

Substantia nigra pars reticulata-works with GPi

2

What does SNc stand for?

Substantia nigra pars compacta

3

What does STN stand for?

Sub thalamic nucleus-modulator of basal ganglia output

4

Apoptosis

Programmed cell death

5

What can the Wt protein do that the mutant protein (expanded form) can't do?

Prevent apoptosis, prevent excitotoxicity, regulate gene transcription, axonal transport, mitochondrial health

6

Why is there more apoptosis in mutant protein?

More PolyQ, leads to more caspase-9= "excecutioners", expanded cells more susceptible to apoptosis

7

Autophagy

Process of aberrant (not normal) organelles breakdown inside autolysosome (isolation membrane-->autophagosome-->lysosome)

8

Mitophagy

Breakdown of mitochondria

9

What happens if lysosomal autophagy is disrupted?

Dysfunction and deregulation

10

Aggregation

Formation of a number of things that form a cluster

11

Aggregation in HD

Caspase-6 site-generates N-terminal fragments (PolyQ) that aggregate in cytoplasm and nucleus (GAIN OF FUNCTION), intracellular

12

Aggregation in AD

Amyloid forms aggregates extracellularly--> amyloid plaques

13

Aggregation in PD (4)

-Alpha-syn. (found in Lewy bodies) forms aggregates
-WT, A30P, & A53T form lipid-based aggregates
-Dysfunction of ubiquitin proteasome system and lysosomal autophagy leads to failure to remove aggregates
-Beta sheets are bad: sticky-->aggregates

14

Excitotoxicity

Process by which nerve cells are damaged or killed by excessive stimulation by NTs, such as glutamate

15

What does excitotoxicity lead to?

Depolarized cell: impaired mitochondrial membrane potential--> more Calcium--> reduced ATP/ADT ration and increased NMDA currents (mimics glutamate)

16

Excitotoxicity in AD

Amyloid beta (plaques) activate astrocytes and microglia--> secretion of toxic cytokines

17

How does normal Whtt protein protect against apoptosis and caspase activation?

-BCL2 is protective of mitochondria from apoptosis
-Does not have more caspase-9 like mutant htt
-Not as susceptible to NMDA toxicity

18

Symptoms of HD and why

Chorea (violent jerking movements) because of the disease favoring direct pathway. Indirect pathway neurons are most affected, which usually prevents unwanted movement

19

Symptoms of AD and why

Decline in memory because of loss of cortex and hippocampus (large pyramidal cells most vulnerable), neuronal death (apoptosis, excitotoxicity, mitochondrial dysfunction, calcium dynamics, inflammation), plaques and tangles

20

Symptoms of PD and why

Resting tremor, rigidity, bradykinesia (slowed movement) or akinesia (lack of movement), postural instability because of loss of DA and SN neurons, DA deficiency in striatum
-Favors indirect pathway

21

Mixed diseases (2)

Dementia with Lewy bodies and HD

22

What causes plaques in AD?

Aggregation of Amyloid Beta

23

What causes tangles in AD?

Taupathy: binds well to itself, rather than microtubules

24

What causes tangles in AD?

Taupathy: binds well to itself, rather than microtubules
-Hyperphosphorylation of Tau

25

Genetic causes of HD

Autosomal dominant, 50/50 chance, caused by mutation in Htt gene, >37 CAG repeats

26

Genetic causes of AD

Autosomal dominant,

27

Genetic causes of AD

Idiopathic (arises from itself), only 5% genetic, APOE4 allele is a risk factor

28

What 3 genes do autosomal dominant genes express in AD?

1. APP
2. Presenilin 1
3. Presenilin 2
(2&3 make up gamma secretase)
All affect amount of Ab42

29

Genetic causes of PD

Alpha-syn. mutation or overexpression, DJ-1, Parkin, PINK-1, LRRK-2
-mutation on chromosome 4 at SCNA gene that codes for alpha-syn.

30

Environmental causes/risks in HD

Environment has no role in creating or decreases risk, genotype=phenotype in HD