Abstract: Novel ApoE peptide derivatives and ApoE-protein transduction domain conjugates are disclosed which are useful for treating disorders including CNS inflammation, traumatic brain injury, inflammatory bowel disease (also known as Crohn's Disease or ulcerative colitis), cerebral ischemia, atherosclerosis, sepsis, multiple sclerosis and arthritic diseases, Alzheimer's Disease and other brain disorders. The invention encompasses methods for protecting subjects having undergone irradiation or radiotherapy by administration of ApoE or at least one ApoE mimetic peptide.