Provided are compounds that target the nucleotide-binding oligomerization domain, leucine rich repeat containing X1 (NLRX1) pathway. The compounds can be used to treat conditions such as autoimmune diseases, allergic diseases, chronic and/or inflammatory central nervous system diseases, chronic and/or inflammatory respiratory diseases, cancer, and infectious diseases. Exemplary conditions include multiple sclerosis, asthma, Alzheimer's disease, Parkinson's disease, neuroinflammation resulting from, for example, stroke, traumatic brain injury, or spinal cord injury, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and inflammatory bowel disease.