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Flashcards in 21: cholesterol Deck (22):
1

cholesterol in brain %? what form? other derivatives?

brain contains 2-5% body mass, but 35% total body cholesterol. predominantly unesterified aka free cholesterol. only small amounts of cholesterol esters. other hydroxylated derivatives like 24 or 27 hydroxychol.

2

cholesterol and BBB? excess cholesterol?

doesn't readily cross BBB. so if you have chol in brain, it was made there. excess chol excreted from brain as 24 - hydroxycholesterol, synthesized by cholesterol 24 - hydroxylase

3

cholesterol 24 hydroxylase: expressed where? not where?

only in a small population of neurons in brain: pyramidal cells of cortex, purkinje cells of cerebellum. not in glial cells.

4

lipoproteins in CNS?

are HDL sized, no LDL in CNS. unesterified cholesterol mostly.

5

in brain: CNS separated from plasma by? this means?

BBB so plasma lipoproteins like LDL can't enter brain from plasma = all CNS cholesterol is made within the CNS

6

which cells synthesize cholesterol?

all cells: neurons and glial

7

major protein in CNS lipoproteins is? synthesized and secreted by?

apo E: synthesized/secreted by glial cells, NOT NEURONS

8

apo E isoforms: what proteins?

E2 = cys + cys at 112 and 158. E3 = cys, arg. E4 = two arg

9

E3 vs. E4 and mechanisms of AD? (4)

E3 promotes axonal growth/repair, E4 doesn't. E4 has defective lipidation. E3 forms complex with AB to enhance degradation, E4 doesn't. E3 protects from apoptosis more than E4.

10

statins as treatment for AD? how?

some studies show it can reduce/delay AD. promote a secretase cleavage of APP = less AB. also some anti inflammatory effects

11

bexarotene: what? effect?

retinoid X receptor agonist, regulates cholesterol metabolism. increases apo E synthesis and thus increases LpE secretion by astrocytes

12

bexarotene conclusion: increases? reduces? improves?

increases apoE and LpE. reduces AB and plaques. improves cognition and memory.

13

bexarotene not effective in?

not effective in Apo E KO mice, so LpE probably involved in the beneficial effect

14

Niemann Pick Type C disease: what inheritance? what is it? what features?

inherited autosomal recessive. neurodegeneration disorder that results in ataxia, seizures, weight loss, death.

15

npc 1 -/- mice: cerebellum?

purkinje cell degeneration

16

npc1 protein? 2?

transmembrane protein, limiting membrane of lysosomes. larger. 2: smaller and soluble in lumen of lysosomes.

17

NPC1 and 2: expression? main action?

expressed in all cells, aka neurons and glial. cholesterol binding proteins

18

elimination of NPC1 only in neurons causes? conclusion?

causes the neurodegneration. this means the phenotype is due to lack of NPC1 in neurons, not glia

19

current therapy for NPC disease?

no effective treatment but cyclodextrin reduces neurodegen in mice: cholesterol sequestring agent. use in low doses like 0.1 mM

20

smith lemli optiz syndrome: what?

severe neurological disorder caused by genetic defect in final enzyme of cholesterol biosynth. pathway

21

smith lemli optiz syndrome: characteristics?

defect in 7 dehydrocholesterol reductase = impaired chol synthesis. polydactylyl, syndactylyl, cleft palate, holoprosencephaly, neurological impairment, premature death

22

smith lemli optiz syndrome fibroblasts: what do you see? causes of SLOS?

low cholesterol, high 7 DHC. developmental problems caused probably by 7DHC cholesterol, not chol deficiency