Psychostimulant-Induced Endoplasmic Reticulum Stress and Neurodegeneration

The endoplasmic reticulum (ER) is a subcellular organelle that ensures proper protein folding process. The ER stress is defined as cellular conditions that disturb the ER homeostasis, resulting in accumulation of unfolded and/or misfolded proteins in the lumen of the ER. The presence of these proteins within the ER activates the ER stress response, known as unfolded protein response (UPR), to restore normal functions of the ER. However, under the severe and/or prolonged ER stress, UPR initiates apoptotic cell death. Psychostimulants such as cocaine, amphetamine, and methamphetamine cause the ER stress and/or apoptotic cell death in regions of the brain related to drug addiction. Recent studies have shown that the ER stress in response to psychostimulants is linked to behavioral sensitization and that the psychostimulant-induced ER stress signaling cascades are closely associated with the pathogenesis of the neurodegenerative diseases. Therefore, this review was conducted to improve understanding of the functional role of the ER stress in the addiction as well as neurodegenerative diseases. This would be helpful to facilitate development of new therapeutic strategies for the drug addiction and/or neurodegenerative diseases caused or exacerbated by exposure to psychostimulants.