Protein aggregation and defective RNA metabolism as mechanisms for motor neuron damage.
CNS Neurol Disord Drug Targets
; 9(3): 285-96, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20406182
ABSTRACT
The presence of protein inclusions within the central nervous system is a characteristic of most neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Aggregates may induce cell death trough several mechanisms, such as sequestration of essential cellular components, clogging of the proteasome system, and/or disruption of axonal transport. The neuropathological signature of ALS is represented by the presence of ubiquitinated inclusions immunoreactive for the protein TDP-43 in the cytoplasm of motor neurons. Recent studies demonstrated that a significant percentage of familial ALS cases are caused by pathogenic mutations in the TAR DNA binding protein and fused in sarcoma/translocated in liposarcoma genes encoding, respectively, for TDP-43 and FUS proteins. Both TDP-43 and FUS are DNA/RNA-binding proteins involved in transcriptional regulation and splicing, shuttling, maturation and transport of mRNA molecules. Mutations in the two genes seem to induce a nucleo-cytoplasmic redistribution of FUS and TDP-43, possibly promoting aggregate formation and/or disrupting their physiological nuclear functions or their interactions with specific RNA targets. Those findings collectively suggest that alterations in cellular RNA metabolism may trigger motor neuron degeneration.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA
/
Esclerose Lateral Amiotrófica
/
Neurônios Motores
/
Degeneração Neural
/
Proteínas do Tecido Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Revista:
CNS Neurol Disord Drug Targets
Assunto da revista:
NEUROLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Itália