Oligodendroglial Process Formation is Differentially Affected by Modulating the Intra- and Extracellular Cholesterol Content

Cholesterol is an essential component of eukaryotic plasma membranes and plays an important role in membrane organization and signaling processes. It is the major lipid component of detergent resistant caveolin-1 containing rafts which previously had been reported as a platform for nerve growth factor (NGF) signaling in oligodendrocytes (OL). Surprisingly, a knockdown of caveolin-1 attenuated the process formation of OL (Schmitz et al. J Neurosci Res 88:572–588, 2010), for which a loss of cholesterol could be responsible. In the present report, we could show that a caveolin-1 knockdown resulted in an elevation of cellular cholesterol level; it may indicate an important role of caveolin-1 in cholesterol trafficking to the plasma membrane. Treatment with exogenous PEG cholesterol, which was incorporated to the plasma membrane, supported oligodendroglial process formation, in particular when OL were stimulated by NGF. In this context we have found that OL express NPC1L1 (Niemann–Pick disease type C1-Like 1) which could modulate cholesterol uptake. In contrast, depletion of membrane-bound cholesterol diminished NGF-induced process formation concomitant with a reduced activity of p42/44 mitogen-activated protein kinases

Scedosporium apiospermum brain abscesses in a patient after near-drowning – a case report with 10-year follow-up and a review of the literature

Scedosporium apiospermum is known to be a fungal pathogen affecting immunocompromised as well as non-immunodeficient patients. Although this fungus is found rarely, an infection can lead to severe and even fatal disease. Here, we describe the case of a 41-year-old female who developed multiple Scedosporium apiospermum brain abscesses after near-drowning with aspiration of contaminated mud and water. She showed various neurological symptoms. The patient recovered after removal of abscesses in combination with long-term antifungal treatment

Infliximab-Associated Chronic Inflammatory Central Nervous System Disease and Peroneal Nerve Injury in a Psoriatic Patient Refractory to Treatment: Case Report with 10-Year Follow-Up

The tumor necrosis factor-α (TNF-α) antagonists infliximab, adalimumab, and etanercept have been approved for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriasis, and psoriatic arthritis. Manifestations of demyelinating disease have been reported for patients receiving TNF-α antagonists. We describe a rare manifestation of a chronic inflammatory process affecting both the central and peripheral nervous system in a patient who received infliximab for the treatment of psoriasis and psoriatic arthritis. Infliximab therapy was discontinued and symptoms improved under high-dose intravenous glucocorticoid pulse therapy

Impact of the cellular prion protein on amyloid-β and 3PO-tau processing.

Previous studies indicate an important role for the cellular prion protein (PrP(C)) in the development of Alzheimer's disease (AD) pathology. In the present study, we analyzed the involvement of PrP(C) in different pathological mechanisms underlying AD: the processing of the amyloid-β protein precursor (AβPP) and its interaction with AβPP, tau, and different phosphorylated forms of the tau protein (p-tau). The effect of PrP(C) on tau expression was investigated in various cellular compartments using a HEK293 cell model expressing a tau mutant (3PO-tau) or wild type (WT)-tau. We could show that PrP(C) reduces AβPP cleavage, leading to decreased levels of Aβ40 and sAβPP without changing the protein expression of AβPP, β-secretase, or γ-secretase. Tau and its phosphorylated forms were identified as interactions partners for PrP(C), raising the question as to whether PrP(C) might also be involved in tau pathology. Overexpression of PrP(C) in PRNP and 3PO-tau transfected cells resulted in a reduction of 3PO-tau and p-tau as well as a decrease of 3PO-tau-related toxicity. In addition, we used the transgenic PrP(C) knockout (Prnp0/0) mouse line to study the dynamics of tau phosphorylation, an important pathological hallmark in the pathogenesis of AD in vivo. There, an effect of PrP(C) on tau expression could be observed under oxidative stress conditions but not during aging. In summary, we provide further evidence for interactions of PrP(C) with proteins that are known to be the key players in AD pathogenesis. We identified tau and its phosphorylated forms as potential PrP-interactors and report a novel protective function of PrP(C) in AD-like tau pathology.peerReviewe