A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level.

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed.

Stability Studies of New Caged bis-deoxy-coelenterazine Derivatives and Their Potential Use as Cellular pH Probes.

The synthesis of new bis-deoxy-coelenterazine (1) derivatives bearing ester protective groups (acetate, propionate and butyrate esters) was accomplished. Moreover, their hydrolytic stability at room temperature was evaluated in dimethylsulfoxide (DMSO) as solvent, using the nuclear magnetic resonance (NMR) spectra of the key products at different time intervals. The results showed an increasing hydrolysis rate according to longest aliphatic chain, with a half-life of 24 days of the more stable acetate derivative (4a).

Engineering REST-Specific Synthetic PUF Proteins to Control Neuronal Gene Expression: A Combined Experimental and Computational Study.

Regulation of gene transcription is an essential mechanism for differentiation and adaptation of organisms. A key actor in this regulation process is the repressor element 1 (RE1)-silencing transcription factor (REST), a transcriptional repressor that controls more than 2000 putative target genes, most of which are neuron-specific. With the purpose of modulating REST expression, we exploited synthetic, designed, RNA binding proteins (RBPs) able to specifically target and dock to REST mRNA.

Activation of Autophagy, Observed in Liver Tissues From Patients With Wilson Disease and From ATP7B-Deficient Animals, Protects Hepatocytes From Copper-Induced Apoptosis.

Background & Aims: Wilson disease (WD) is an inherited disorder of copper metabolism that leads to copper accumulation and toxicity in the liver and brain. It is caused by mutations in the adenosine triphosphatase copper transporting β gene (ATP7B), which encodes a protein that transports copper from hepatocytes into the bile. We studied ATP7B-deficient cells and animals to identify strategies to decrease copper toxicity in patients with WD.