Cdk5 is a key factor in tau aggregation and tangle formation in vivo.
Neuron
; 38(4): 555-65, 2003 May 22.
Article
en En
| MEDLINE
| ID: mdl-12765608
ABSTRACT
Tau aggregation is a common feature of neurodegenerative diseases such as Alzheimer's disease, and hyperphosphorylation of tau has been implicated as a fundamental pathogenic mechanism in this process. To examine the impact of cdk5 in tau aggregation and tangle formation, we crossed transgenic mice overexpressing the cdk5 activator p25, with transgenic mice overexpressing mutant (P301L) human tau. Tau was hyperphosphorylated at several sites in the double transgenics, and there was a highly significant accumulation of aggregated tau in brainstem and cortex. This was accompanied by increased numbers of silver-stained neurofibrillary tangles (NFTs). Insoluble tau was also associated with active GSK. Thus, cdk5 can initiate a major impact on tau pathology progression that probably involves several kinases. Kinase inhibitors may thus be beneficial therapeutically.
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Banco de datos:
MEDLINE
Asunto principal:
Tronco Encefálico
/
Corteza Cerebral
/
Ovillos Neurofibrilares
/
Proteínas tau
/
Quinasas Ciclina-Dependientes
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Neuron
Asunto de la revista:
NEUROLOGIA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos