The disulfide isomerase Grp58 is a protective factor against prion neurotoxicity.

Prion diseases are transmissible neurodegenerative disorders characterized by extensive neuronal apoptosis and accumulation of misfolded prion protein (PrP(SC)). Recent reports indicate that PrP(SC) induces neuronal apoptosis via activation of the endoplasmic reticulum (ER) stress pathway and activation of the ER resident caspase-12. Here, we investigate the relationship between prion replication and induction of ER stress during different stages of the disease in a murine scrapie model.

Prion replication alters the distribution of synaptophysin and caveolin 1 in neuronal lipid rafts.

The main event in the pathogenesis of prion diseases is the conversion of the cellular prion protein (PrP(C)) into the abnormal, protease-resistant prion protein (PrP(res)). PrP(C) is a GPI-anchored protein located in lipid rafts or detergent-resistant membranes (DRMs). Here we describe the association of PrP with DRMs in neuronal cell bodies and axons during the course of murine scrapie and its relation with the distribution of the PrP-interacting proteins caveolin 1 and synaptophysin.

Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein.

Prion diseases are characterized by accumulation of misfolded prion protein (PrP(Sc)), and neuronal death by apoptosis. Here we show that nanomolar concentrations of purified PrP(Sc) from mouse scrapie brain induce apoptosis of N2A neuroblastoma cells. PrP(Sc) toxicity was associated with an increase of intracellular calcium released from endoplasmic reticulum (ER) and up-regulation of several ER chaperones.

Changes in the glycosylation pattern of prion protein in murine scrapie. Implications for the mechanism of neurodegeneration in prion diseases.

In prion diseases, the normal prion protein (PrP(c)) undergoes a conformational change that results in the abnormal form, named scrapie prion protein (PrP(sc)). The visual system of rodents provides a relatively simple neuronal model in which the cell bodies of neurons are confined to the retina and the axons constitute the optic nerve. We investigated by Western blot the profile of PrP(c) in the optic nerve and retina of normal hamsters and mice.

Non-nuclear histone H1 is upregulated in neurones and astrocytes in prion and Alzheimer's diseases but not in acute neurodegeneration.

A non-nuclear isoform of histone H1 is constitutively expressed in neurones. This protein is the major lipopolysaccharide (LPS)-binding protein in the brain. Since the major systemic LPS-binding protein is released in the liver and is an acute phase reactant, we were interested to learn whether this novel CNS histone showed altered expression following neuronal injury.

Inflammatory response and retinal ganglion cell degeneration following intraocular injection of ME7.

Scrapie is a prion disease which occurs naturally in sheep and which can be transmitted experimentally to rodents. After intracerebral injection of ME7 into mouse, an atypical inflammatory response, characterized by T-lymphocytes and activated microglia is present early in the course of the disease. In the present work, we have investigated the relationship between this inflammatory response, astrocytosis and neuronal loss along the visual pathway after intraocular injection (intraocular) of ME7 in C57BL/6J mice.

Factors affecting the survival of cat retinal ganglion cells after optic nerve injury.

After partial transection of one optic nerve in adult cats the majority of beta retinal ganglion cells degenerate and die 1 week after axotomy, whilst other cell classes degenerate slowly and survive for a long period after the lesion. We have investigated the effects of intravitreal and intraperitoneal injections of MK-801, a NMDA-glutamate receptor antagonist, on the early degeneration of retinal ganglion cells after partial optic nerve section. Control animals received saline intravitreal injections.

The ganglion cell response to optic nerve injury in the cat: differential responses revealed by neurofibrillar staining.

The early responses of cat retinal ganglion cells to axotomy have been examined using neurofibrillar and Nissl-stained wholemounts. We were interested to learn whether the enhanced neurofilament expression, seen in a number of neuronal systems, was also present in different neuronal populations of the cat retina and could be used to study the distribution of these cells. We found that beta ganglion cells degenerate very rapidly after axotomy with the nuclei becoming pyknotic within a few days.