Results: Although JNK activation was observed following 3-NP administration, the results

indicate that the lack of JNK3 does not confer Navitoclax concentration neuroprotection against 3-NP toxicity. Thus, other pathways must be involved in the neurodegeneration induced in this model. One of the possible pathways towards 3-NP-induced apoptosis could involve the calpains, as their activity was increased in wild-type and Jnk3-null mice. Conclusion: Although JNK3 is a key protein involved in cell death in different neurodegenerative diseases, the present study demonstrates that the lack of JNK3 does not confer neuroprotection against 3-NP-induced neuronal death. “
“M. Gessi, J. Hammes, L. Lauriola, E. Dörner, J. Kirfel, G. Kristiansen, A. zur Muehlen, D. Denkhaus, A. Waha and T. Pietsch (2013) Neuropathology and Applied Neurobiology39, 417–425 GNA11 and N-RAS mutations: alternatives for MAPK pathway activating GNAQ mutations in primary melanocytic tumours of the central

nervous system Aim: Primary melanocytic tumours are uncommon neoplasms of the central nervous system. Although similarities with uveal melanomas have been hypothesized, data on their molecular features are limited. Methods: In this study, we investigated the mutational PD-0332991 cell line status of BRAFV600E, KIT, GNAQ, GNA11, N-RAS and H-RAS in a series of 19 primary melanocytic tumours of the central nervous system (CNS). Results: We identified six cases harbouring mutations in the hotspot codon 209 of the GNAQ gene and two cases with mutations in the hotspot codon 209 of the GNA11 gene. Two mutations in codon 61 of N-RAS were also found. In the single strand conformation polymorphism (SSCP) analysis, no shifts corresponding to BRAFV600E mutations or suggesting activating mutations in the KIT gene were observed. Conclusions: In primary melanocytic tumours of the CNS, GNA11 and N-RAS mutations

represent a mechanism of MAPK pathway activation Cyclin-dependent kinase 3 alternative to the common GNAQ mutations. On the other hand, BRAFV600E mutations and activating KIT mutations seem to be absent or very rare in these tumours. “
“Amyloid plaques, a well-known hallmark of Alzheimer’s disease (AD), are formed by aggregated β-amyloid (Aβ). The cellular prion protein (PrPc) accumulates concomitantly with Aβ in amyloid plaques. One type of amyloid plaque, classified as a neuritic plaque, is composed of an amyloid core and surrounding dystrophic neurites. PrPc immunoreactivity reminiscent of dystrophic neurites is observed in neuritic plaques. Proteinase K treatment prior to immunohistochemistry removes PrPc immunoreactivity from amyloid plaques, whereas Aβ immunoreactivity is enhanced by this treatment. In the present study, we used a chemical pretreatment by a sarkosyl solution (0.1% sarkosyl, 75 mM NaOH, 2% NaCl), instead of proteinase K treatment, to evaluate PrPc accumulation within amyloid plaques.