Project Details
Projekt
RP7: Investigation of novel mechanisms in degradation of aggregated neuroserpin
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2007 to 2015
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 35615435
Neuronal accumulation of mal-processed proteins is the hallmark of a number of neurodegenerative disorders such as diffuse Lewy body diseases, tauopathies and familial encephalopathy with neuroserpin inclusion bodies (FENIB). Some of these diseases share common pathways leading to neuronal death, which are linked to accumulation of proteins in specific intracellular compartments. Accumulation of malprocessed neuroserpin reflects a dynamic process, resulting from the disturbed balance between synthesis and degradation. During the first funding period we were able to recapitulate the pathogenic characteristics such as aggregation, degradation, and neurodegeneration in a mouse model for FENIB.The objective of our proposal is to identify components involved in the degradation of aggregated neuronal proteins. We have generated a Caenorhabditis elegans model for FENIB by expressing fluorescently tagged, aggregation-prone forms of the neuroserpin homolog SRP-2. This model allows us to screen for novel modulators and pharmalogical substances modulating the degradation of aggregated SRP-2, which will be further investigated in mammalian cell culture experiments and transgenic neuroserpin expressing mice. Data from these studies will be valuable in identifying novel therapeutical strategies for dementias in general.
DFG Programme
Research Units
Subproject of
FOR 885:
Neuronal Protein Turnover
