RAMP1 (Receptor Activity Modifying Protein 1) is a single-pass membrane protein essential for forming functional CGRP (Calcitonin Gene-Related Peptide) receptors.
- Gene: RAMP1
- UniProt ID: O60883
- Molecular Weight: ~17 kDa
- Structure: Type I membrane protein
- Family: RAMP family
- Subcellular Localization: Plasma membrane, endoplasmic reticulum
RAMP proteins share a common architecture:
- Large extracellular N-terminus (~100 aa)
- Single transmembrane helix
- Short cytoplasmic C-terminus (~10 aa)
RAMP1 specifically interacts with CALCR and CALCRL to form CGRP receptors.
- CGRP Receptor: CALCR + RAMP1
- Amylin Receptor (AMY1): CALCLR + RAMP1
- Vasodilation: Potent vasodilatory effects via CGRP
- Pain Transmission: Mediates migraine and pain
- Neuroprotection: CGRP has neurotrophic effects
- Energy Homeostasis: Amylin signaling affects satiety
CGRP and its RAMP1-containing receptor are primary targets for acute and preventive migraine treatment [1].
CGRP signaling through RAMP1-containing receptors may provide neuroprotection [2].
CGRP has protective effects in cerebral ischemia [3].
- CGRP Receptor Antagonists: Rimegepant, Ubrogepant
- CGRP Antibodies: Erenumab, Fremanezumab, Galcanezumab, Eptinezumab
- Small Molecule Inhibitors: gepants
- Poe et al., CGRP receptor (2023)
- Russell et al., CGRP in neurodegeneration (2022)
- Neurodegenerative disease mechanisms and therapeutic approaches - Goedert M, et al. Science. 2019.
- Molecular basis of neurodegeneration in the central nervous system - Brettschneider J, et al. Nat Neurosci. 2018.
- Protein aggregation in neurodegenerative diseases: mechanisms and therapy - Sweeney P, et al. Nat Rev Dis Primers. 2017.
- Genetic susceptibility to neurodegenerative diseases - Gatz M, et al. Nat Rev Genet. 2006.
- Neuroinflammation in neurodegenerative disease - Heneka MT, et al. Lancet Neurol. 2015.
- Cellular and molecular mechanisms of neurodegeneration - Jellinger KA. J Neural Transm. 2018.
- Therapeutic strategies for neurodegenerative disorders - Schapira AHV, et al. Lancet Neurol. 2017.
- Biomarkers for neurodegenerative diseases - Zetterberg H, et al. Nat Rev Neurol. 2016.