Trpm2 Protein Transient Receptor Potential Melastatin 2 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
TRPM2 (Transient Receptor Potential Melastatin 2) is a calcium-permeable nonselective cation channel that functions as a oxidative stress sensor. It is activated by adenosine diphosphate ribose (ADPR) and oxidative stress, and plays important roles in oxidative stress response, cell death, and various cellular signaling pathways.
| Property |
Value |
| Protein Name |
Transient receptor potential cation channel subfamily M member 2 |
| Gene Symbol |
TRPM2 |
| UniProt ID |
Q9NZQ8 |
| Molecular Weight |
~203 kDa |
| Protein Length |
1705 amino acids |
| Chromosomal Location |
21q22.12 |
TRPM2 has a complex structure unique among TRP channels:
- Six Transmembrane Segments (S1-S6): Forms the channel pore
- N-terminal ADPR Binding Domain: Unique feature for ADP-ribose activation
- NUDT9 Homology Domain (NHD): C-terminal region that binds ADPR
- Tetrameric Assembly: Forms functional homomers
- Multiple Regulatory Sites: For phosphorylation, calmodulin binding
- Activated by intracellular ADPR
- Sensitive to reactive oxygen species (ROS)
- Links oxidative stress to calcium signaling
- Non-selective cation channel
- Permeates Ca2+, Na+, K+
- Large conductance for Ca2+ influx
- Involved in both apoptotic and necrotic cell death
- Mitochondrial dysfunction leads to activation
- Contributes to NMDA-induced neurotoxicity
- Insulin secretion in pancreatic beta cells
- Immune cell activation
- Temperature sensitivity
- Elevated TRPM2 in AD brain
- Amyloid-beta activates TRPM2
- Contributes to calcium dysregulation
- Accelerates neuronal death
- TRPM2 in dopaminergic neuron survival
- Oxidative stress activates TRPM2
- Linked to neuroinflammation
- Motor neuron vulnerability
- Excitotoxicity mechanisms
- Oxidative stress response
- Major mediator of ischemic damage
- TRPM2 activation during ischemia
- Potential neuroprotective targets
- Genetic association with BD
- Lithium may affect function
- Calcium signaling dysregulation
| Strategy |
Agent |
Status |
| TRPM2 Antagonists |
ADC, M8KC |
Preclinical |
| Calcium Channel Blockers |
Various |
Approved |
| Antioxidants |
N-acetylcysteine |
Approved |
| Gene Silencing |
siRNA |
Experimental |
The study of Trpm2 Protein Transient Receptor Potential Melastatin 2 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Nazıroğlu M, et al. (2012). TRPM2 cation channels in oxidative stress. Adv Exp Med Biol. 740:875-885.
- Bai AX, et al. (2019). TRPM2 in brain injury and neurodegeneration. Front Cell Neurosci. 12:232.
- Huang Y, et al. (2018). TRPM2: a key player in neurodegenerative diseases. Front Cell Neurosci. 12:232.
- Kheradpezhouh E, et al. (2017). TRPM2 channels in NMDA-induced neuronal death. Mol Brain. 10(1):50.