Abstract
Stress is well-known to contribute to the development of many psychiatric illnesses including alcohol and substance use disorder (AUD and SUD). The deleterious effects of stress have also been implicated in the acceleration of biological age, and age-related neurodegenerative disease. The physio-pathology of stress is regulated by the corticotropin-releasing factor (CRF) system, the upstream component of the hypothalamic-pituitary-adrenal (HPA) axis. Extensive literature has shown that dysregulation of the CRF neuroendocrine system contributes to escalation of alcohol consumption and, similarly, chronic alcohol consumption contributes to disruption of the stress system. The CRF system also represents the central switchboard for regulating homeostasis, and more recent studies have found that stress and aberrations in the CRF pathway are implicated in accelerated aging and age-related neurodegenerative disease. Corticotropin releasing factor binding protein (CRFBP) is a secreted glycoprotein distributed in peripheral tissues and in specific brain regions. It neutralizes the effects of CRF by sequestering free CRF, but may also possess excitatory function by interacting with CRF receptors. CRFBP’s dual role in influencing CRF bioavailability and CRF receptor signaling has been shown to have a major part in the HPA axis response. Therefore, CRFBP may represent a valuable target to treat stress-related illness, including: development of novel medications to treat AUD and restore homeostasis in the aging brain. This narrative review focuses on molecular mechanisms related to the role of CRFBP in the progression of addictive and psychiatric disorders, biological aging, and age-related neurodegenerative disease. We provide an overview of recent studies investigating modulation of this pathway as a potential therapeutic target for AUD and age-related neurodegenerative disease.
Highlights
The deleterious effect of stress, both as an acute insult or chronic exposure, has been linked to many pathophysiological changes in the human body
As stress has been well established to play a role in the pathogenesis of various neuropsychiatric disorders, many studies over the years have focused on targeting the corticotropin-releasing factor (CRF) system to mediate dysregulation of the HPA axis (Binder and Nemeroff, 2010; Haass-Koffler and Bartlett, 2012)
Various peptides within the CRF system have been investigated as potential targets for treatment, have shown limited efficacy in clinical translation
Summary
The deleterious effect of stress, both as an acute insult or chronic exposure, has been linked to many pathophysiological changes in the human body. Translational efforts in the AUD field have contributed to evaluating the role of CRF binding protein (CRFBP) as a potential target to modulate the stress system (Haass-Koffler, 2018; Figure 1). We will review the role of CRFBP as a potential target for treating other SUD, anxiety, depression, and some neurodegenerative disorders.
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