Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As manifestations of prion diseases include disturbances of hypothalamic and pituitary functions, we tested the hypothesis that the cellular prion protein (PrPC) has a role as modulator of the hypothalamic-pituitary-adrenal axis. The level of corticosterone and adrenocorticotropic hormone were compared in PrPC null (PrP 0/0) and wild-type (PrP+/+) mice. PrP 0/0 showed hypercorticism during the dark part of day. After acute stress, corticosterone and adrenocorticotropic hormone increased similarly in PrP+/+ and PrP 0/0 mice. Adrenocorticotropic hormone, however, remained elevated in PrP+/+ 0/0 mice at corticosterone levels that are inhibitory in PrP mice. Pretreatment with corticosterone or dexamethasone inhibited stress-induced elevation of adrenocorticotropic hormone in PrP+/+ but not in PrP 0/0 mice. Thus, PrPC may play a role in the negative feedback regulation of axis.
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PMID:Hypothalamic-pituitary-adrenal axis disregulation in PrPC-null mice. 1879

During acute stress in the endoplasmic reticulum (ER), mammalian prion protein (PrP) is temporarily prevented from translocation into the ER and instead routed directly for cytosolic degradation. This "pre-emptive" quality control (pQC) system benefits cells by minimizing PrP aggregation in the secretory pathway during ER stress. However, the potential toxicity of cytosolic PrP raised the possibility that persistent pQC of PrP contributes to neurodegeneration in prion diseases. Here, we find evidence of ER stress and decreased translocation of nascent PrP during prion infection. Transgenic mice expressing a PrP variant with reduced translocation at levels expected during ER stress was sufficient to cause several mild age-dependent clinical and histological manifestations of PrP-mediated neurodegeneration. Thus, an ordinarily adaptive quality-control pathway can be contextually detrimental over long time periods. We propose that one mechanism of prion-mediated neurodegeneration involves an indirect ER stress-dependent effect on nascent PrP biosynthesis and metabolism.
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PMID:Reduced translocation of nascent prion protein during ER stress contributes to neurodegeneration. 1880 31