VEGF alleviates ALS-CSF induced cytoplasmic accumulations of TDP-43 and FUS/TLS in NSC-34 cells.
J Chem Neuroanat
; 81: 48-52, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28163215
Cytoplasmic mislocalisation and aggregation of TDP-43 and FUS/TLS proteins in spinal motor neurons contribute to the pathogenesis of the highly fatal disorder amyotrophic lateral sclerosis (ALS). We investigated the neuroprotective effect of VEGF on expression of these proteins in the motor neuronal cell line NSC-34 modelled to reminisce sporadic form of ALS. We studied the expression of TDP-43 and FUS/TLS proteins after exposure to ALS-CSF and following VEGF supplementation by quantitative confocal microscopy and electron microscopy. ALS-CSF caused cytoplasmic overexpression of both the proteins and stress-granule formation in the cells. These alterations were alleviated by VEGF supplementation. The related ultrastructural changes like nuclear membrane dysmorphism and p-bodies associated changes were also reversed. However the protein expression did not completely translocate to the nucleus, as some cells continued to show to cytoplasmic mislocalisation. Thus, the present findings indicate that VEGF alleviates TDP43 and FUS pathology by complimenting its role in controlling apoptosis and reversing choline acetyl transferase expression. Hence, VEGF appears to target multiple pathogenic processes in the neurodegenerative cascade of ALS.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Citoplasma
/
Proteína FUS de Unión a ARN
/
Factor A de Crecimiento Endotelial Vascular
/
Proteínas de Unión al ADN
/
Esclerosis Amiotrófica Lateral
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Chem Neuroanat
Asunto de la revista:
ANATOMIA
/
NEUROLOGIA
/
QUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Países Bajos