0000000000240296
AUTHOR
Carsten Saft
P08 Analysis of Nrf2-downstream targets after fumarate treatment in dorsal root ganglia—an anti-inflammatory therapy in neurodegenerative disease?!
Background Dimethylfumarate (DMF) is a new disease modifying therapy. Several studies have shown convincing data after DMF therapy in both autoimmune inflammatory diseases and neurodegenerative disorders like Huntington9s disease (HD). DMF exerts neuroprotective effects via induction of the nuclear factor E2-related factor 2 (Nrf2) and detoxification pathways. Although the exact mechanisms that lead to neurodegeneration are not fully understood the contribution of oxidative stress inducing neurodegeneration is assumed. Aims To analyse the effects of DMF on axonal growth and regeneration and to describe the influence of DMF on the Nrf2-pathway. Methods/techniques We thus investigated the eff…
A protein quality control pathway regulated by linear ubiquitination.
Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence doma…