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Ca<sub>V</sub>2.1 mediates presynaptic dysfunction induced by amyloid β oligomers

3 months 1 week ago
Synaptic dysfunction is an early pathological phenotype of Alzheimer's disease (AD) that is initiated by oligomers of amyloid β peptide (Aβ(o)s). Treatments aimed at correcting synaptic dysfunction could be beneficial in preventing disease progression, but mechanisms underlying Aβ(o)-induced synaptic defects remain incompletely understood. Here, we uncover an epithelial sodium channel (ENaC) - Ca(V)2.3 - protein kinase C (PKC) - glycogen synthase kinase-3β (GSK-3β) signal transduction pathway...
Alexander F Jeans

Targeted degradation of α-Synuclein using an evolved botulinum toxin protease

3 months 1 week ago
There is considerable interest in the targeted degradation of proteins implicated in human disease. The use of sequence-specific proteases for this purpose is severely limited by the difficulty in engineering the numerous enzyme-substrate interactions required to yield highly selective proteases while maintaining catalytic activity. Herein, we report a strategy to evolve a protease for the programmed degradation of α-Synuclein, a presynaptic protein closely linked to Parkinson's disease. Our...
Philipp Sondermann