Structure and Biological Synthesis

• Calcitonin Gene-Related Peptide (CGRP) is a 37 amino acid neuropeptide in two forms: α-CGRP and β-CGRP.
• α-CGRP is mainly localized in the central and enteric peripheral nervous systems.
• β-CGRP is expressed through alternative splicing of the calcitonin gene.
• CGRP receptors involve several proteins, including calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1), necessary for functional CGRP receptor.

Physiological Functions and Distribution

• Involved in various physiological processes:
• Dilates blood vessels, maintaining blood flow and vascular smooth muscle tone.
• Acts as a neuropeptide in the nervous system, modulating pain and sensory signalling.
• Present in large numbers in the central and peripheral nervous systems, especially in sensory neurons, trigeminal ganglia, and dorsal root ganglia.
• Projects to other organs, including: the cardiovascular system, gastrointestinal tract, and skin.
• Regulates inflammation, immune response, and tissue repair.

Role in Migraine Pathophysiology

• Connection with migraines has revolutionized understanding of this condition.
• During migraines, CGRP levels elevate in peripheral and central nervous systems, causing neurogenic inflammation, vasodilation, and enhanced pain transmission.
• Release from trigeminal nerve endings triggers events leading to migraine symptoms like severe headache, sensitivity to light and sound, and nausea.
• Led to development of targeted therapies, including CGRP receptor antagonists (gepants) and monoclonal antibodies against CGRP or its receptor, showing effectiveness in migraine prevention and treatment.

Therapeutic Applications and Drug Development

• Identification of CGRP's role in migraine has led to new therapeutic strategies.
• Several classes of CGRP-targeted medications have been created and used in clinical practice:
• Monoclonal antibodies like erenumab, fremanezumab, and galcanezumab for preventing migraine attacks.
• Small molecule CGRP receptor antagonists like ubrogepant and rimegepant for acute treatment.
• Investigation of CGRP-targeted therapies for other diseases such as: cluster headaches, osteoarthritis, and inflammatory diseases.
• These medications represent advancements in neurological-specific therapies, providing hope for patients with previously intractable conditions.

Suitable ELISA Kits

• CGRP ELISA Kit
• Calcitonin Gene Related Peptide ELISA Kit