Abstract
Calcitonin gene-related peptide has emerged as a therapeutic target in migraine. Monoclonal antibodies and small molecule receptor antagonists (gepants) directed against CGRP have been approved or are in Phase II or III clinical trials. For monitoring the long-term safety of these drugs, it is helpful to consider the role of CGRP in brain functioning. Qualitative review of the preclinical literature on CGRP in brain physiology and pathophysiology. Within the brain, CGRP is upregulated by stresses such as ischemia, injury, hyperthermia, and seizure, and activates neuroprotective processes. Thus, CGRP buffers intracellular calcium, triggers antiapoptotic signaling, upregulates a number of neurotrophins (including insulin-like growth factor-1/IGF-1, basic fibroblast growth factor/bFGF, and nerve growth factor/NGF), reduces brain edema, and likely increases antioxidant defenses. When released outside the blood-brain barrier, CGRP likely protects the endothelium, upregulates growth factor signaling from the endothelium to the brain parenchyma, strengthens the blood-brain barrier, protects the immune privilege of the brain by inhibiting the movement of neutrophils and monocytes, and facilitates neurogenesis and angiogenesis at stem cell niches. CGRP participates in a wide range of neuroprotective processes. In theory, migraineurs with comorbid brain pathology might be at increased risk from CGRP inhibition. However, the extent of compensating processes is unknown and will determine whether these risks materialize in practice.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.