deltaFosBs

deltaFosB is a protein isoform produced from the FosB gene. It is a truncated form of the FosB protein, lacking the C-terminal DNA-binding and dimerization domains. This structural difference significantly impacts its function. deltaFosB is a transcription factor that plays a crucial role in neuronal plasticity and the long-term adaptation of the brain to chronic stimuli.

Unlike other Fos proteins that are rapidly induced and degraded in response to acute stimuli, deltaFosB is remarkably stable. This stability is attributed to its unique structure, which prevents its degradation. Consequently, deltaFosB can accumulate in neurons over time with repeated exposure to certain environmental factors, particularly those associated with reward and addiction, such as drugs of abuse and chronic stress.

The accumulation of deltaFosB in specific brain regions, notably the nucleus accumbens and dorsal striatum, is thought to underlie the persistent changes in gene expression that contribute to the transition from acute drug effects to long-term addiction. It can activate or repress the transcription of a variety of target genes, altering neuronal circuitry and behavioral responses. Research suggests that deltaFosB's persistent presence can stabilize adaptations in neural circuits, making them resistant to change and contributing to the enduring nature of addiction. Its role is also being investigated in other forms of behavioral adaptation, including learning and memory, and in neurological disorders.