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CGRP and Brain Functioning: Cautions for Migraine Treatment.
1Department of Psychology, University of Maine, Orono, ME, USA.
Headache
|July 23, 2019
Summary
Calcitonin gene-related peptide (CGRP) plays a vital neuroprotective role in the brain. Understanding CGRP
Area of Science:
- Neuroscience
- Pharmacology
- Migraine Research
Background:
- Calcitonin gene-related peptide (CGRP) is a key therapeutic target for migraine treatment.
- Approved monoclonal antibodies and gepants targeting CGRP are in clinical trials.
- Long-term safety monitoring necessitates understanding CGRP's role in brain function.
Purpose of the Study:
- To review preclinical literature on CGRP's function in brain physiology and pathophysiology.
- To inform the safety assessment of CGRP-targeting migraine therapies.
Main Methods:
- Qualitative review of preclinical studies.
- Focus on CGRP's role in brain physiology and pathophysiology.
Main Results:
- CGRP is upregulated by brain stresses like ischemia and seizure, activating neuroprotective mechanisms.
- It buffers calcium, triggers antiapoptotic signals, upregulates neurotrophins (IGF-1, bFGF, NGF), reduces edema, and enhances antioxidant defenses.
- Outside the blood-brain barrier, CGRP protects endothelium, strengthens barrier integrity, maintains immune privilege, and promotes neurogenesis and angiogenesis.
Conclusions:
- CGRP is integral to numerous neuroprotective processes within the brain.
- Migraine patients with existing brain conditions may face risks from CGRP inhibition.
- The clinical significance of these risks depends on the extent of compensatory mechanisms, which remain to be fully elucidated.
Keywords:
calcitonin gene-related peptideischemic strokemigrainemultiple sclerosisoxidative stresstraumatic brain injuryMore Related Videos
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