What is myelin according to Dr. Drewes?
Extension of lipid membrane of Oligodendrocyte cells that covers axons.
What is myelin composed of?
Lipid (70%) & Protein (30%)
Is myelin ester-linked or ether-linked?
Ether-linked
What 6 prominent proteins are found in CNS myelin?
- MBP (myelin basic protein)
- PLP (proteolipid protein)
- CNP (cyclic neucotide P-ase)
- MAG (Myelin associated glyprot)
- MOG (Myelin-Oligoden. Glycoprot)
- OMgp (Oligoden.-Myelin-Glycoprot)
(only memorize the first three, because the rest all contain “myelin” in the name)
What are the two proteins that are different in PNS myelin compared to CNS?
- P0(P0prot) instead of PLP
- 7th protein = PMP-22
What does MBP do in the CNS myelin?
“Glues” together the first and second lipid bilary when they come close.
What does PLP do in the CNS myelin?
Brings together extracellular components of 2nd lipid bilayer and on.
-PLP is a membrane spanning protein that has affinity for other PLPs on the other membranes
Where is cholesterol present in myelin?
Both leaflets of the lipid bilayer.
Extracellular - Galactose/sulfoGalactose
Intracellular - P-inositol/P-serine
What does it mean when Dr. Drewes says that “Myelin is inert.”?
- formed when we are young
- very low turnover
- recent studies actually indicate that there is some activity
What cells give rise (are precursors) to oligodendrocytes?
OPCs
Why do OPCs remain in the adult brain long after myelination is complete?
OPCs make oligodendrocytes in adult brain in response to injury/demyelinating diseases (e.g. MS).
What is the difference between demyelinating and dysmyelinating?
- Demyelinating:
- have normal myelin, but then some disease leads to breakdown
- Dysmyelinating:
- the myelin was never formed right to begin with –> defective due to inherited genetic mutation
Experimental Allergic Encephalomyelitis (EAE) is a model for what common disease?
MS
Experimental Allergic Neuritis (EAN) is a model for what disease?
Guillain-Barré Syndrome
(immunity against peripheral components of myelin)
Where is the mutation in adrenoleukodystrophy that allows synthesis of long chain fatty acids, but is blocked by Lorenzo’s Oil?
ABC transporter
What does PLP do in myelin?
Acyl groups make it lipid soluble
What is the result if any of the exons in Myelin Basic Protein (MBP) are misread?
Myelin disorder
(result of gene duplication or overproduction)
What creates the water accumulations that MRI scans detect in MS lesion?
Demyelination –> breakdown of lipid & proteins –> less lipid means more water present due to less fat
What allows white blood cells to attach and penetrate blood vessels after stimulation by cytokines?
Vascular Cell Adhesion Molecule
What does Mab do in treatment of MS with Natalizumab?
Blocks immune cells from getting into the brain!
(antibody against alpha-4-beta-1 receptor on white blood cell)