Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.21.64 (
proteinase K
)
4,071
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response,
heat shock factor 1
(
HSF1
), would play an important role in prion disease. Uninoculated
HSF1
knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions
HSF1
KO mice had a dramatically shortened lifespan, succumbing to disease approximately 20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in
HSF1
KO and control mice. The accumulation of
proteinase K
(PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus,
HSF1
provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease.
...
PMID:Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease. 1875 33
