| Affiliation |
(AGL) Chairman, Department of Ophthalmology, The Methodist Hospital, Houston, Texas; Professor of Ophthalmology, Weill Cornell Medicine, New York City, New York; (SF) Baylor College of Medicine, Houston, Texas |
| Transcript |
Alright, today I'm going to talk to you a little bit about gangliosides and how they apply in neuro-ophthalmology. You don't have to know everything about ganglioside, but you need to know what it is and how it can relate to downstream autoimmune disease through a process called molecular mimicry. And molecular mimicry comes up a lot in terms of autoimmune conditions in neuro-opth that are precipitated by infectious diseases as a trigger. And so just very briefly, what we're trying to do in terms of making the ganglioside or the cerebroside or the globoside is get to the core molecules and these two core molecules are extremely important because they have multiple functions across multiple cellular interactions: both cell signaling and membrane formation, and the immune response. And so, when you make sphingosine, you're really starting off with amino acids like serine and palmityl CoA and then through a series of redox reactions, you get to this core molecule. When you convert that to the waxy ester that's the ceramide and the ceramide is what's going to end up being the backbone of the sides and they're called sides because we're adding something on to the side. A series of sugars is going to be added onto here and if you have just a glucose or galactose, a single sugar, that ceramide plus that single sugar is what we call a cerebroside, so it'd be a glucose cerebroside or galactose cerebroside. However, if you add a neutral sugar on there like GalNac, that's a globoside but the one we're talking about today is ganglioside. And what makes a ganglioside a ganglioside is the addition of an oligosaccharide chain and that's formed by N-acetyl neuraminic acid, and it just takes too long to say that, so we just call it sialic acid. And you remember our old friend sialic acid because the sialac acid is also the thing on the red cell membrane that produces the negative zeta potential that allows these dimentation rate to be measure of inflammatory disease and it's the same thing, scialic acid, NANA. So, if we have one of these NANA's, that is a ganglioside because we have the ceramide core, the associated sugars in a certain sequence; in this case, these four sugars lined up and one little triangle and that triangle equals NANA. And if we have two of these guys, that's going to be ganglioside disialic acid. If you have three of these guys, that's going to be ganglioside trisialic acid. And if we have four of these guys, that is ganglio side quatro. And because the core backbone has this configuration here, that's going to be a number one configuration. If we lop off this one, that's going to be making it a bigger number. So each time we takeoff one of these core sugars, we're going to be reducing it from a1, a2, and a3. So this happens to be a 1 because it has all the sugars in the backbone and, because we have four scialic acids, that's a quatro. And then, we have two series which are basically rows: the A row and the B row. So for example, in this example, we have ceramide, the core sugar backbone, that's ganglioside, we have four scialic acids so that's quatro, we got the one configuration, and we have the B series, and that's going to characterize GQ1b.And the reason you need to know about GQ1b is this same configuration is highly conserved and so bacteria use the same configuration by accident in their glycoprotein coats and their lipopolysaccharide code. And the one that causes the cross reaction, the molecular mimicry, is Campylobacter jejuni so it just so happens that the Campylobacter jejuni's lipopolysaccharide look very similar to the ganglioside and so when we're testing for diseases where people have autoimmune molecular mimicry after Campylobacter jejuni diarrhea, they might get Guillain Barre syndrome and the Miller Fisher variant, and you can watch the video on those two conditions. But this piece of it is what's causing the molecular mimicry so you don't need to know everything about gangliosides but you do need to know the core molecules, sphingosine, ceramide, how we add the sugars, make the sides, and how that side might look exactly like Campylobacter jejuni. |
