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NeuroNetwork 12


Project title: Autophagy mechanisms in stress-induced neuro- and psychopathology

Project leader: Anne Albrecht, Anke Müller


cCBBS Albrecht mini

Autophagy in lysosomes is one of the major pathways for cellular protein degradation. Disturbances in these processes are particularly devastating for neuronal cells, leading to protein accumulation to toxic levels with subsequent functional impairments and neuronal loss. Such processes are involved in the pathogenesis of neurodegenerative diseases and measures to enhance autophagic flux have been, therefore, implicated in counteracting Alzheimer’s and Parkinson’s diseases, for instance.

However, recent studies demonstrate that autophagy may play a much broader role in the brain’s response to external challenges: while on a cellular level autophagy promotes cytoprotection and the maintenance of synaptic function under stress in vitro, autophagy in vivo is associated with the success of various antidepressive treatments in the context of stress-induced psychopathologies.

However, the exact mechanisms of autophagy contributions to synapse development and function as well as to stress resilience on a cellular and neuronal network level are not well understood. Therefore, in the current project, we will investigate fundamental molecular and cellular mechanisms of autophagy by utilizing neuronal cell cultures in vitro and their role in an established stress model in vivo. Using different cellular stress models, we set out to analyse molecular mechanisms of autophagy dynamics and their impact on protein translation in vitro. Identified molecular candidates will be then tested for a regulation of the response to stress on a behavioural level in vivo. Thereby, we hope to reveal starting points for a pharmacological treatment of autophagy-dependent diseases of the nervous system.

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