Myelin biogenesis: Dynamics of MBP, PLP and galactolipids

Hande Ozgen

Myelin biogenesis: Dynamics of MBP, PLP and galactolipids

Vertaalde titel van de bijdrage: Biogenese van Myeline: Dynamiek van MBP, PLP en galactolipiden

Hande Ozgen

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De aanmaak en het onderhoud van myeline membranen vereisen een nauwgezette regulering van complexe intracellulaire transportroutes, die zorg dragen voor het transport van myeline lipiden en eiwitten naar hun eindbestemming, waar ze hun functie kunnen uitoefenen. Omdat de functie van myeline eiwitten en lipide nauw verbonden is met hun lokalisatie kan elke verandering daarin gepaard gaan met ingrijpende veranderingen in de vorming van deze gespecialiseerde membranen. Zo zijn bijvoorbeeld de lokalisatie en organisatie van myeline specifieke componenten ontregeld in de ziekte multiple sclerose (MS) en is de aanmaak van ‘nieuwe’ myeline verstoord. Dit wordt onder meer veroorzaakt door een veranderding in de omgeving van cellen die verantwoordelijk zijn voor die aanmaak.
Het in dit proefschrift beschreven onderzoek heeft nieuw en gedetailleerd inzicht gegeven in de mechanismen die het transport, lokalisatie, en laterale organisatie in het membraan van de belangrijkste myeline eiwitten PLP en MBP reguleren. Daarbij zijn effecten van intracellulaire componenten zoals de myeline galactolipiden, galactosylceramide en sulfatide onderzocht maar ook de invloed van cellulaire omgevingsfactoren, zoals fysologische en ziekte-geassocieerde extracellulaire matrix eiwitten en pro-inflammatoire cytokines. De verkregen kennis draagt bij aan het beter begrijpen waarom de (her)aanmaak en het onderhoud van myeline faalt in MS, en biedt daardoor perspectief voor het verder ontwikkelen van therapeutische mogelijkheden voor een ziekte waarvan het ontstaan nog grotendeels onbekend is.

Vertaalde titel van de bijdrage	Biogenese van Myeline: Dynamiek van MBP, PLP en galactolipiden
Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Hoekstra, Dick, Supervisor Baron, Wia, Co-supervisor Kahya, Neriman, Co-supervisor
Datum van toekenning	15-sep.-2014
Plaats van publicatie	[S.l.]
Uitgever	[S.n.]
Gedrukte ISBN's	978-90-367-7236-5
Elektronische ISBN's	978-90-367-7235-8
Status	Published - 2014

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Complete dissertationSubmitted manuscript, 11 MB
Title and contentsFinal publisher's version, 146 KB
Chapter 1Final publisher's version, 486 KB
Chapter 2Final publisher's version, 1,05 MB
Chapter 3Final publisher's version, 2,81 MB
Chapter 4Final publisher's version, 1,82 MB
Chapter 5Final publisher's version, 2,48 MB
Chapter 6Final publisher's version, 3,29 MB
Chapter 7Final publisher's version, 317 KB
PropositionsFinal publisher's version, 85,7 KB

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title = "Myelin biogenesis: Dynamics of MBP, PLP and galactolipids",

abstract = "Myelin membrane biogenesis and maintenance require a tight regulation of complex intracellular trafficking machineries, involving appropriate and sequential transportation of major myelin lipids and proteins to their final destination, where they can exert their function. As the function of major myelin lipids and proteins are closely related with their localization, any alteration in the itinerary of biosynthesis and transportation of these molecules might dramatically change the biogenesis of these specialized membranes. For example, in demyelinating diseases such as MS, the localization and organization of myelin specific components are perturbed, leading to (de novo) myelin biogenesis failure, caused, among others, by an altered extracellular environment.The work described in this thesis has provided new and detailed insight into mechanisms that regulate the trafficking, localization and lateral organization of the major myelin proteins PLP and MBP in response to intrinsic elements, such as the myelin typical galactolipids galactosylceramide and sulfatide, and extrinsic elements, such as physiological and disease-associated extracellular matrix proteins and pro-inflammatory cytokines. The obtained knowledge improves our understanding why biogenesis or maintenance of myelin fails in MS, thereby contributing to the elucidation of potential repair mechanisms, which is crucial for the development of an effective therapeutic approach in MS.",

author = "Hande Ozgen",

year = "2014",

language = "English",

isbn = "978-90-367-7236-5",

publisher = "[S.n.]",

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T1 - Myelin biogenesis

T2 - Dynamics of MBP, PLP and galactolipids

AU - Ozgen, Hande

PY - 2014

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N2 - Myelin membrane biogenesis and maintenance require a tight regulation of complex intracellular trafficking machineries, involving appropriate and sequential transportation of major myelin lipids and proteins to their final destination, where they can exert their function. As the function of major myelin lipids and proteins are closely related with their localization, any alteration in the itinerary of biosynthesis and transportation of these molecules might dramatically change the biogenesis of these specialized membranes. For example, in demyelinating diseases such as MS, the localization and organization of myelin specific components are perturbed, leading to (de novo) myelin biogenesis failure, caused, among others, by an altered extracellular environment.The work described in this thesis has provided new and detailed insight into mechanisms that regulate the trafficking, localization and lateral organization of the major myelin proteins PLP and MBP in response to intrinsic elements, such as the myelin typical galactolipids galactosylceramide and sulfatide, and extrinsic elements, such as physiological and disease-associated extracellular matrix proteins and pro-inflammatory cytokines. The obtained knowledge improves our understanding why biogenesis or maintenance of myelin fails in MS, thereby contributing to the elucidation of potential repair mechanisms, which is crucial for the development of an effective therapeutic approach in MS.

AB - Myelin membrane biogenesis and maintenance require a tight regulation of complex intracellular trafficking machineries, involving appropriate and sequential transportation of major myelin lipids and proteins to their final destination, where they can exert their function. As the function of major myelin lipids and proteins are closely related with their localization, any alteration in the itinerary of biosynthesis and transportation of these molecules might dramatically change the biogenesis of these specialized membranes. For example, in demyelinating diseases such as MS, the localization and organization of myelin specific components are perturbed, leading to (de novo) myelin biogenesis failure, caused, among others, by an altered extracellular environment.The work described in this thesis has provided new and detailed insight into mechanisms that regulate the trafficking, localization and lateral organization of the major myelin proteins PLP and MBP in response to intrinsic elements, such as the myelin typical galactolipids galactosylceramide and sulfatide, and extrinsic elements, such as physiological and disease-associated extracellular matrix proteins and pro-inflammatory cytokines. The obtained knowledge improves our understanding why biogenesis or maintenance of myelin fails in MS, thereby contributing to the elucidation of potential repair mechanisms, which is crucial for the development of an effective therapeutic approach in MS.

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SN - 978-90-367-7236-5

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Myelin biogenesis: Dynamics of MBP, PLP and galactolipids

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