MENINGES AS AN OVERLOOKED TARGET FOR GLOBOID CELL LEUKODISTROPHY
type: CreativeWork
description: Globoid cell leukodystrophy (GLD), also known as Krabbe disease, is a severe neurological disorder caused by the deficiency of galactocerebrosidase (GALC) enzyme, leading to the accumulation of toxic metabolites and ultimately resulting in progressive demyelination and neurodegeneration. The only treatment option currently available is the hematopoietic stem/progenitor cell transplant (HSPC-T), although this is not effective if administered after diseases onset. Thus, there is no cure for GLD emphasizing the need for novel approaches. While most of the GLD neurodegenerative clues in the brain have been clarified, the underlying mechanisms of neuroinflammation are not yet fully understood. GLD brain shows an important inflammatory infiltration including the accumulation of unique and often multinucleated macrophages (“globoid cells”). However, the role in GLD pathogenesis and progression of all other non-parenchymal components of the brain, potentially contributing to the inflammatory process and diseases progression, has not been elucidated yet. Recently, new and important interactions between brain and meninges have been described. Meninges appeared as a highly heterogeneous tissue with trophic, immune and neurogenic properties. Recently it has been identified a neurogenic stem/progenitor cell (NSPC) population present in meninges. In vivo, meningeal NPCs can migrate to the brain and, without proliferation, differentiate into functional integrated neurons of the cortex. Following brain pathological conditions, meninges are activated increasing their immune function and neural stem cell properties. However, the potential involvement of meninges during GLD pathogenesis and progression is completely unknown. In this project, I have studied the involvement of meninges in the pathogenesis and progression of GLD in the Twitcher mouse model that resembles the early infantile form in humans. I have used mice at four different time points that represent the disease stages, …
abstract: Globoid cell leukodystrophy (GLD), also known as Krabbe disease, is a severe neurological disorder caused by the deficiency of galactocerebrosidase (GALC) enzyme, leading to the accumulation of toxic metabolites and ultimately resulting in progressive demyelination and neurodegeneration. The only treatment option currently available is the hematopoietic stem/progenitor cell transplant (HSPC-T), although this is not effective if administered after diseases onset. Thus, there is no cure for GLD emphasizing the need for novel approaches. While most of the GLD neurodegenerative clues in the brain have been clarified, the underlying mechanisms of neuroinflammation are not yet fully understood. GLD brain shows an important inflammatory infiltration including the accumulation of unique and often multinucleated macrophages (“globoid cells”). However, the role in GLD pathogenesis and progression of all other non-parenchymal components of the brain, potentially contributing to the inflammatory process and diseases progression, has not been elucidated yet. Recently, new and important interactions between brain and meninges have been described. Meninges appeared as a highly heterogeneous tissue with trophic, immune and neurogenic properties. Recently it has been identified a neurogenic stem/progenitor cell (NSPC) population present in meninges. In vivo, meningeal NPCs can migrate to the brain and, without proliferation, differentiate into functional integrated neurons of the cortex. Following brain pathological conditions, meninges are activated increasing their immune function and neural stem cell properties. However, the potential involvement of meninges during GLD pathogenesis and progression is completely unknown. In this project, I have studied the involvement of meninges in the pathogenesis and progression of GLD in the Twitcher mouse model that resembles the early infantile form in humans. I have used mice at four different time points that represent the disease stages, …
author: AMENTA, ALESSIA
language: eng
date published: 2025-01-21
date modified: 2026-07-27T20:19:05Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

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property ID: Handle
value: https://hdl.handle.net/2434/1123715