0000000000680698
AUTHOR
Julia Bär
showing 3 related works from this author
Preventing Jacob-induced transcriptional inactivation of CREB protects synapses from β-amyloid in Alzheimer’s Disease
2020
Abstract Disruption of transcriptional activity of cAMP–responsive element-binding protein (CREB), a master regulator of cell survival and plasticity-related gene expression, is a hallmark of Alzheimer’s disease (AD). CREB shut-off results in early synaptic dysfunction, contributes to AD pathology and eventually neuronal cell death and is elicited by amyloid-β (Aβ)-induced activation of extrasynaptic N-methyl-D-aspartate-receptors (NMDAR). In previous work we found that the protein messenger Jacob encodes and transduces the synaptic or extrasynaptic origin of NMDAR signals to the nucleus. In response to cell survival and plasticity-related synaptic NMDAR stimulation macromolecular transport…
Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis
2019
CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aim…
Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis
2019
CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong impairment of the lysosomal-autophagy machinery. In mice and humans CTSD dysfunction underlies the congenital variant (CLN10) of neuronal ceroid lipofuscinosis (NCL). NCLs are distinct lysosomal storage disorders (LSDs) sharing various hallmarks, namely accumulation of protein aggregates and ceroid lipofuscin leading to neurodegeneration and blindness. The most established and clinically approved approach to treat LSDs is enzyme replacement therapy (ERT) aim…