Ganglioside formation

Summary

The video discusses gangliosides and their significance in neuro-ophthalmology, highlighting their role in autoimmune diseases through molecular mimicry. It explains the synthesis of gangliosides from amino acids and ceramides, detailing the addition of sugars to form different types of gangliosides. The video emphasizes the importance of the GQ1b ganglioside and its molecular mimicry with Campylobacter jejuni, which can trigger autoimmune responses such as Guillain-Barré syndrome. Understanding this molecular mimicry is crucial for diagnosing and managing related autoimmune conditions.

Takeaways

• 🧠 Gangliosides are crucial in neuro-ophthalmology and have multiple functions in cellular interactions, cell signaling, membrane formation, and immune response.
• 🔍 Molecular mimicry is a process where the immune system mistakenly attacks the body's own tissues due to similarities with infectious agents, often triggering autoimmune conditions.
• 🌐 The core molecules of gangliosides are formed from amino acids like serine and palmitate through a series of redox reactions, leading to the ceramide backbone.
• 🍬 Gangliosides are characterized by the addition of an oligosaccharide chain to the ceramide backbone, which includes sialic acid, a key component in the immune response.
• 📚 The term 'ganglioside' comes from the addition of 'side' (sugar) to the ceramide backbone, with different types based on the number and sequence of sugars added.
• 🔑 Ganglioside GQ1b is significant because its structure is highly conserved and resembles the glycoprotein coats and lipopolysaccharide coats of certain bacteria, leading to molecular mimicry.
• 🦠 Campylobacter jejuni is a bacterium whose lipopolysaccharide closely resembles the structure of ganglioside GQ1b, causing an autoimmune response known as molecular mimicry.
• 🚑 Autoimmune diseases like Guillain-Barré syndrome and the Miller Fisher variant can be triggered by molecular mimicry following Campylobacter jejuni infections.
• 🔬 Understanding the core structure of gangliosides and their resemblance to certain bacterial components is essential for diagnosing and treating related autoimmune diseases.
• 📈 The script emphasizes the importance of recognizing the molecular structure of gangliosides for identifying the root cause of autoimmune diseases precipitated by infections.
• 🔍 The distinction between different gangliosides, such as mono-, di-, tri-, and tetra-sialo gangliosides, is based on the number of sialic acids present in their structure.

Q & A

What is the main topic of the video script?

The main topic of the video script is gangliosides, their structure, and their role in neuro-ophthalmology, particularly in relation to autoimmune diseases triggered by molecular mimicry.

What is molecular mimicry and why is it significant in autoimmune diseases?

Molecular mimicry is a phenomenon where a foreign substance, such as a bacterium, has a molecular structure that closely resembles the host's own molecules. This similarity can trigger an autoimmune response, where the immune system mistakenly attacks the host's own tissues, leading to autoimmune diseases.

What are the core molecules of gangliosides and why are they important?

The core molecules of gangliosides are ceramide and the associated sugars. They are important because they are involved in multiple cellular interactions, including cell signaling, membrane formation, and immune response.

How are gangliosides synthesized from ceramide?

Gangliosides are synthesized from ceramide by adding a series of sugars. The addition of an oligosaccharide chain, formed by N-acetylneuraminic acid (also known as sialic acid), distinguishes gangliosides from other types of glycosphingolipids.

What is the difference between a cerebroside and a ganglioside?

A cerebroside is formed by the addition of a single sugar (glucose or galactose) to ceramide. A ganglioside, on the other hand, has an oligosaccharide chain with multiple sialic acids added to the ceramide backbone.

What is the significance of the term 'GQ1b' in the script?

GQ1b refers to a specific type of ganglioside with a ceramide core, four sialic acids (Quattro), and a particular B Series configuration. It is significant because it is highly conserved and can cause molecular mimicry with certain bacterial glycoproteins or lipopolysaccharides.

Which bacterium is mentioned in the script as an example of molecular mimicry with gangliosides?

Campylobacter jejuni is mentioned as an example of a bacterium that has a lipopolysaccharide structure similar to the ganglioside GQ1b, leading to molecular mimicry and potential autoimmune reactions.

What are the potential autoimmune diseases that can be triggered by molecular mimicry after Campylobacter jejuni infection?

Autoimmune diseases that can be triggered by molecular mimicry after Campylobacter jejuni infection include Guillain-Barré syndrome and the Miller Fisher variant.

What is the role of sialic acid in gangliosides and red blood cells?

In gangliosides, sialic acid is part of the oligosaccharide chain that distinguishes them. In red blood cells, sialic acid contributes to the negative zeta potential, which is important for measuring inflammatory disease through sedimentation rates.

How does the addition of sialic acids affect the classification of gangliosides?

The number of sialic acids added to the ceramide backbone determines the classification of gangliosides. For example, one sialic acid forms a ganglioside (GM1), two form GD1a, three form GD1b, and four form GT1b.

What is the significance of the 'numbering' system in gangliosides (e.g., GM1, GD1a, GD1b)?

The numbering system in gangliosides indicates the number of sialic acids present in the oligosaccharide chain. It also reflects the sequential removal of core sugars from the backbone, which affects the ganglioside's structure and function.

Outlines

00:00

🧠 Gangliosides and Neuro-Ophthalmology

This paragraph introduces the topic of gangliosides and their relevance in neuro-ophthalmology, focusing on their role in autoimmune diseases through molecular mimicry. It explains the process of ganglioside synthesis starting from amino acids and leading to the formation of the core molecule, ceramide. The paragraph also details the addition of sugars to form gangliosides and the significance of sialic acid in this process. It highlights the importance of understanding the core structure and the potential for molecular mimicry, particularly in relation to Campylobacter jejuni, which can trigger autoimmune responses in the nervous system.

Keywords

💡Gangliosides

Gangliosides are a type of glycosphingolipid with one or more sialic acids linked on the sugar chain. They play a crucial role in neuro-ophthalmology by participating in cell signaling and membrane formation. The video discusses how gangliosides can lead to autoimmune diseases through molecular mimicry.

💡Neuro-ophthalmology

Neuro-ophthalmology is a subspecialty that merges the fields of neurology and ophthalmology, focusing on visual problems related to the nervous system. The video highlights the relevance of gangliosides in this field, especially regarding autoimmune diseases triggered by infections.

💡Molecular mimicry

Molecular mimicry is a mechanism where infectious agents trigger autoimmune responses because their molecular structures resemble host molecules. The video explains how gangliosides can mimic bacterial lipopolysaccharides, leading to conditions like Guillain-Barré syndrome.

💡Ceramide

Ceramide is a lipid molecule that forms the backbone of gangliosides. It is produced from amino acids like serine and palmitate CoA through redox reactions. The video mentions ceramide as the starting point for synthesizing gangliosides and other related molecules.

💡Sialic acid

Sialic acid, specifically N-acetylneuraminic acid, is a component of gangliosides that contributes to their function and immunogenicity. The video explains its role in forming the oligosaccharide chain in gangliosides and its significance in molecular mimicry.

💡Campylobacter jejuni

Campylobacter jejuni is a bacterium whose lipopolysaccharides can mimic gangliosides, leading to autoimmune responses. The video discusses how this molecular mimicry can result in diseases like Guillain-Barré syndrome following infection with Campylobacter jejuni.

💡Guillain-Barré syndrome

Guillain-Barré syndrome is an autoimmune disorder where the immune system attacks the peripheral nervous system. The video highlights its connection to gangliosides through molecular mimicry, particularly following infections like Campylobacter jejuni.

💡Miller Fisher variant

The Miller Fisher variant is a form of Guillain-Barré syndrome characterized by ataxia, areflexia, and ophthalmoplegia. The video mentions this variant in the context of gangliosides and molecular mimicry, illustrating how infections can trigger specific autoimmune responses.

💡Autoimmune diseases

Autoimmune diseases occur when the immune system mistakenly attacks the body's own cells. The video focuses on how gangliosides can be involved in such diseases through molecular mimicry, especially in the context of neuro-ophthalmology.

💡Redox reactions

Redox reactions involve the transfer of electrons between molecules, playing a key role in the synthesis of ceramide from amino acids. The video briefly touches on these reactions as part of the process of forming the core molecules for gangliosides.

Highlights

Introduction to gangliosides and their application in neuro-ophthalmology.

The importance of understanding gangliosides in relation to downstream autoimmune diseases.

Explanation of molecular mimicry in the context of autoimmune conditions triggered by infectious diseases.

The process of making gangliosides from amino acids through a series of redox reactions.

The role of ceramide as the backbone of gangliosides and its formation.

The addition of sugars to ceramide to form various types of gangliosides.

The distinction between cerebroside and globoside based on the type of sugar added.

The definition and formation of ganglioside with the addition of an oligosaccharide chain.

The significance of sialic acid in the structure of gangliosides and its role in inflammatory disease.

The composition of ganglioside with four sialic acids, referred to as ganglioside IV.

Differentiation between ganglioside series A and B based on the core sugar backbone configuration.

The specific characterization of GQ1b ganglioside and its relevance in molecular mimicry.

The high conservation of the GQ1b configuration and its accidental similarity in bacterial glycoproteins.

The role of Campylobacter jejuni in causing cross-reactions and molecular mimicry with gangliosides.

The connection between autoimmune molecular mimicry after Campylobacter jejuni diarrhea and neurological syndromes.

The potential for testing diseases related to molecular mimicry and the importance of understanding gangliosides.

Transcripts

all right today I'm going to talk to you

a little bit about gangliosides and how

they apply in neuro-ophthalmology you

know have to know everything about

gangly aside 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 naraka

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 ganglia side or the

cerebral side or the global side 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 makes pinga seen you're really

starting off with amino acids like

serine and palmitate co a 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 cerebral side so it'd be a

glucose Arriba side or galactose reverse

side however if you add a neutral sugar

on there like gal Mac that's a globocide

but the one we're talking about today is

gangly side and what makes a ganglia

side and ganglia side is the addition of

an oligosaccharide chain and that's

formed by n acetyl neuro Minich acid and

it just takes too long to say that so we

just call its I Alec and you remember

our old friend sialic acid because the

silac acid is also the thing on the red

cell membrane that produces the negative

zeta potential that allows the

sedimentation rate to be

measure of inflammatory disease and it's

the same thing sciatic acid Dannan so if

we have one of these Nana's that is a

gangly side 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 gonna be

ganglia side die cyanic acid if you have

three of these guys that's going to be

English side try cyanic acid and if we

have for these guys that is ganglia side

cuatro 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 take

off one of these core sugars we're going

to be reducing it from a1 a2 a3 so this

happens to be a 1 because it has all the

sugars in the backbone and because we

have for sciatic acids that's a Quattro

and then we have 2 Series which are

basically ROS the a row and the B row

so for example in this example we have

ceramide the core sugar backbone that's

ganglia side we have for sciatic acids

that's Quattro we got the one

configuration and we have the B Series

and that's going to characterize GQ 1b

and the reason you need to know about GQ

1b 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 x' lipopolysaccharide look very

similar to the ganglia sign and so when

we're testing for diseases where people

have autoimmune molecular mimicry after

Campylobacter jejuni diarrhea they might

get yeon vorrei syndrome

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 ganglia sides

but you do new need to know the core

molecules swing the scene ceramide how

we add the sugars make the sides and how

that side might look exactly like

Campylobacter jejuni