Role of Erk1/2 activation in prion disease pathogenesis: absence of CCR1 leads to increased Erk1/2 activation and accelerated disease progression.
J Neuroimmunol
; 196(1-2): 16-26, 2008 May 30.
Article
in En
| MEDLINE
| ID: mdl-18396336
ABSTRACT
Prion diseases are neurodegenerative infections with gliosis and vacuolation. The mechanisms of degeneration remain unclear, but chemokines may be important. In current experiments CCR1 knock-out (KO) mice succumbed more rapidly to scrapie infection than WT controls. Infected KO mice had upregulation of CCL3, a CCR1 ligand, and CCR5, a receptor with specificity for CCL3. Both infected KO and WT mice had upregulation of CCR5-mediated signaling involving activation of Erk1/2 in astrocytes; however, activation was earlier in KO mice suggesting a role in pathogenesis. In both mouse strains activation of the Erk1/2 pathway may lead to astrocyte dysfunction resulting in neurodegeneration.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Expression Regulation
/
Prion Diseases
/
PrPSc Proteins
/
Mitogen-Activated Protein Kinase 3
/
Receptors, CCR1
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
J Neuroimmunol
Year:
2008
Document type:
Article
Affiliation country:
United States