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Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD+ loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP106–126. NAD+ supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD+ supplementation in PrP106–126-incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival. Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP106–126 are partially dependent on SARM1 NADase activity. This pathway has potential as a therapeutic target in the early stages of prion disease.

To gain insight into the conformational conversion of ovine prion protein (OvPrPC) at different pH values and/or in the presence of CuCl2, the secondary structure of OvPrPC was analysed by circular dichroism (CD) spectroscopy. Copper treatment of OvPrPC under moderately acidic conditions (pH ∼5.0–6.0) as well as physiological conditions (pH 7.4) also makes OvPrPC adopt protease-resistant and β-sheet-rich conformation. However, under lower pH conditions (2.0–4.5) with copper treatment, OvPrPC gained higher α-helix structure. This study demonstrated that Cu2+ can significantly modulate conformational conversion triggered by acidic pH, and this will provide therapeutic intervention approaches for prion diseases. [ABSTRACT FROM PUBLISHER]

Susceptibility to natural scrapie in sheep is associated with polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene. To assess the risk of scrapie in sheep raised in China, DNA from 30 sheep of two breeds was isolated, amplified and sequenced for the PrP gene. The ovine PrP gene was found to be highly homogenous. The genotype associated with high susceptibility to scrapie (VRQ) was absent, whereas that associated with the resistance (ARR) was present in 6.7% of sheep examined. ARK was also rare (6.7%). ARQ that is associated with an intermediate susceptibility was the genotype observed in the most of sheep examined (86.6%). These data suggest that Chinese sheep of Mongolian sheep breed are susceptible to scrapie. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzes the association of apoptosis inducing factor (AIF) signal pathways in interferon-γ in promoting apoptosis of the human acute monocytic cell line (THP-1) that occurs in the early phase of infection caused by Mycobacterium bovis.