Task Particle Radiation-Induced Dysregulation of Protein Homeostasis in the Brain (Completed)
Last Published:  07/31/19 10:05:33 AM (Central)
Short Title: Brain Protein Homeostasis
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Other:
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Solicited
Aims:
In this proposal, we plan to conduct in-depth investigations of those cellular pathways that regulate the removal of damaged proteins, repair of DNA damage, and response to conditions of oxidative stress through protein modifications in the brain. Protein modification by ubiquitin is a highly regulated process that is catalyzed by specific enzyme families that are capable of modifying the correct protein in the correct cellular location at the correct time in order to control important processes such as the maintenance of genomic stability, cell cycle progression, removal of damaged or misfolded proteins, impaired autophagy, apoptosis, and gene transcription. Depending on the radiation dose and beam quality, particle radiation may cause significant damage to proteins and oxidative stress in the cells in the central nervous system, leading to dysfunction of the cellular ubiquitin-related pathways, an increase in the levels of extracellular ubiquitin and persistent subsequent downstream effects on regulation of stress-associated signaling pathways in many different cell types within the CNS, precipitating neurodegenerative disease.

We hypothesize that quantitative changes in cellular ubiquitin pools occur when neuronal cells are exposed to particle radiation and aim to study the impact of protein degradation after particle radiation using both in vitro and in vivo model systems.
Resources (None Listed)
Mappings
RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
GapCBS-CNS - 1: Are there significant adverse changes in CNS performance in the context and time scale of spaceflight operations? If so, how is significance defined, and which neuropsychological domains are affected? Is there a significant probability that space radiation exposure would result in adverse changes? What are the pathways and mechanisms of change?
GapCBS-CNS - 2: Does space radiation exposure elicit key events in adverse outcome pathways associated with neurological diseases? What are the key events or hallmarks, their time sequence and their associated biomarkers (in-flight or post-flight)?
GapCNS - 6: How can new knowledge and data from molecular, cellular, tissue and animal models of late CNS risks or clinical human data be used to estimate late CNS risks to astronauts from GCR and SPE?
You are here!TaskParticle Radiation-Induced Dysregulation of Protein Homeostasis in the Brain

RiskRisk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders
You are here!TaskParticle Radiation-Induced Dysregulation of Protein Homeostasis in the Brain