The Rapid Exchange of Zinc (2+) Enables Trace Levels to Profoundly Influence Amyloid-beta Misfolding and Dominates Assembly Outcomes in Cu (2+)/Zn (2+) Mixtures

This work was supported by the Biotechnology and Biological Sciences Research Council Project GrantBB/M023877/1 and Quota Studentship

Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease

Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition

A specific role for hippocampal mossy fiber's zinc in rapid storage of emotional memories

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Activation of metabotropic glutamate receptor type 2/3 supports the involvement of the hippocampal mossy fiber pathway on contextual fear memory consolidation

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Differential needs of zinc in the CA3 area of dorsal hippocampus for the consolidation of contextual fear and spatial memories

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Anisomycin injection in area CA3 of the hippocampus impairs both short-term and long-term memories of contextual fear

International audienceProtein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal area CA1 or CA3 immediately after contextual fear conditioning. As previously shown, injections in CA1 impaired long-term memory but spared short-term memory. Conversely, injections in CA3 impaired both long-term and short-term memories. We conclude that early steps of experience-induced plasticity occurring in CA3 and underlying short-term memory require protein synthesis