Axonal pathology in Krabbe's disease: The cytoskeleton as an emerging therapeutic target.
J Neurosci Res
; 94(11): 1037-41, 2016 11.
Article
em En
| MEDLINE
| ID: mdl-27638589
ABSTRACT
In Krabbe's disease (KD), demyelination and myelin-independent axonal and neuronal defects contribute to the severe neuropathology. The toxic substrate that accumulates in this disease, psychosine, induces alterations in membrane lipid rafts with downstream consequences to cellular signaling pathways that include impaired protein kinase C, ERK, and AKT-glycogen synthase kinase-3ß (GSK3ß) activation. In addition to impaired recruitment of signaling proteins to lipid rafts, endocytosis and axonal transport are affected in KD. Defects in AKT-GSK3ß activation, a central pathway regulating microtubule stability, together with alterations in neurofilaments and microtubules and severely defective axonal transport, highlight the importance of the neuronal cytoskeleton in KD. This Review critically discusses these primary neuronal defects as well as new windows for action opened by their identification that may contribute to effectively correct the neuropathology that underlies this disorder. © 2016 Wiley Periodicals, Inc.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Axônios
/
Citoesqueleto
/
Leucodistrofia de Células Globoides
/
Neurônios
Idioma:
En
Revista:
J Neurosci Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Portugal