The Transient Receptor Potential Melastatin 2 (TRPM2) Channel Contributes to β-Amyloid Oligomer-Related Neurotoxicity and Memory Impairment

Overview

Journal J Neurosci

Specialty Neurology

Date 2015 Nov 13

PMID 26558786

Citations 76

Authors

Valeriy G Ostapchenko

Megan Chen

Monica S Guzman

Yu-Feng Xie

Natalie Lavine

Jue Fan

Flavio H Beraldo

Amanda C Martyn

Jillian C Belrose

Yasuo Mori

John F Macdonald

Vania F Prado

Marco A M Prado

Michael F Jackson

Affiliations

Soon will be listed here.

Abstract

Significance Statement: Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress sensing calcium-permeable channel that is thought to contribute to calcium dysregulation associated with neurodegenerative diseases, including Alzheimer's disease. Here we show that oligomeric β-amyloid, the toxic peptide in Alzheimer's disease, facilitates TRPM2 channel activation. In mice designed to model Alzheimer's disease, genetic elimination of TRPM2 normalized deficits in synaptic markers in aged mice. Moreover, the absence of TRPM2 improved age-dependent spatial memory deficits observed in Alzheimer's mice. Our results reveal the importance of TRPM2 for neuronal toxicity and memory impairments in an Alzheimer's mouse model and suggest that TRPM2 could be targeted for the development of therapeutic agents effective in the treatment of dementia.

Citing Articles

Deletion of the Transient Receptor Potential Melastatin 2 Gene Mitigates the 6-Hydroxydopamine-Induced Parkinson's Disease-Like Pathology.

Ferreira A, Ulrich H, Mori Y, Feng Z, Sun H, Britto L Mol Neurobiol. 2024; 62(4):5333-5346.

PMID: 39541072 DOI: 10.1007/s12035-024-04611-9.

Inhibiting endoplasmic reticulum stress alleviates perioperative neurocognitive disorders by reducing neuroinflammation mediated by NLRP3 inflammasome activation.

Meng F, Song J, Huang X, Zhang M, Sun X, Jing Q CNS Neurosci Ther. 2024; 30(10):e70049.

PMID: 39432407 PMC: 11493103. DOI: 10.1111/cns.70049.

Melatonin: A potential nighttime guardian against Alzheimer's.

Zhang Z, Xue P, Bendlin B, Zetterberg H, De Felice F, Tan X Mol Psychiatry. 2024; 30(1):237-250.

PMID: 39128995 PMC: 11649572. DOI: 10.1038/s41380-024-02691-6.

Targeting Transient Receptor Potential Melastatin-2 (TRPM2) Enhances Therapeutic Efficacy of Third Generation EGFR Inhibitors against EGFR Mutant Lung Cancer.

Chen Z, Vallega K, Boda V, Quan Z, Wang D, Fan S Adv Sci (Weinh). 2024; 11(35):e2310126.

PMID: 39044361 PMC: 11425210. DOI: 10.1002/advs.202310126.

Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury.

Huang P, Qu C, Rao Z, Wu D, Zhao J Front Immunol. 2024; 15:1391355.

PMID: 39007141 PMC: 11239348. DOI: 10.3389/fimmu.2024.1391355.

References

Mattson M, Pedersen W, Duan W, Culmsee C, Camandola S . Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases. Ann N Y Acad Sci. 2000; 893:154-75. DOI: 10.1111/j.1749-6632.1999.tb07824.x. View

Wang H, Lee D, Dandrea M, Peterson P, Shank R, Reitz A . beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology. J Biol Chem. 2000; 275(8):5626-32. DOI: 10.1074/jbc.275.8.5626. View

Kuo Y, Kokjohn T, Watson M, Woods A, Cotter R, Sue L . Elevated abeta42 in skeletal muscle of Alzheimer disease patients suggests peripheral alterations of AbetaPP metabolism. Am J Pathol. 2000; 156(3):797-805. PMC: 1876838. DOI: 10.1016/s0002-9440(10)64947-4. View

Ikonomidou C, Stefovska V, Turski L . Neuronal death enhanced by N-methyl-D-aspartate antagonists. Proc Natl Acad Sci U S A. 2000; 97(23):12885-90. PMC: 18859. DOI: 10.1073/pnas.220412197. View

Rammsayer T . Effects of pharmacologically induced changes in NMDA-receptor activity on long-term memory in humans. Learn Mem. 2001; 8(1):20-5. PMC: 311354. DOI: 10.1101/lm.33701. View

Kim H, Russell R, Raina A, Harris P, Siedlak S, Zhu X . Protein disulfide isomerase in Alzheimer disease. Antioxid Redox Signal. 2001; 2(3):485-9. DOI: 10.1089/15230860050192260. View

Perraud A, Fleig A, Dunn C, Bagley L, Launay P, Schmitz C . ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature. 2001; 411(6837):595-9. DOI: 10.1038/35079100. View

Farber N, Kim S, Dikranian K, Jiang X, Heinkel C . Receptor mechanisms and circuitry underlying NMDA antagonist neurotoxicity. Mol Psychiatry. 2002; 7(1):32-43. DOI: 10.1038/sj.mp.4000912. View

Walsh D, Klyubin I, Fadeeva J, Cullen W, Anwyl R, Wolfe M . Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002; 416(6880):535-9. DOI: 10.1038/416535a. View

10.

Yasuda Y, Kudo T, Katayama T, Imaizumi K, Yatera M, Okochi M . FAD-linked presenilin-1 mutants impede translation regulation under ER stress. Biochem Biophys Res Commun. 2002; 296(2):313-8. DOI: 10.1016/s0006-291x(02)00859-8. View

11.

LaFerla F . Calcium dyshomeostasis and intracellular signalling in Alzheimer's disease. Nat Rev Neurosci. 2002; 3(11):862-72. DOI: 10.1038/nrn960. View

12.

Kraft R, Grimm C, Grosse K, Hoffmann A, Sauerbruch S, Kettenmann H . Hydrogen peroxide and ADP-ribose induce TRPM2-mediated calcium influx and cation currents in microglia. Am J Physiol Cell Physiol. 2003; 286(1):C129-37. DOI: 10.1152/ajpcell.00331.2003. View

13.

Jankowsky J, Xu G, Fromholt D, Gonzales V, Borchelt D . Environmental enrichment exacerbates amyloid plaque formation in a transgenic mouse model of Alzheimer disease. J Neuropathol Exp Neurol. 2003; 62(12):1220-7. DOI: 10.1093/jnen/62.12.1220. View

14.

Aarts M, Iihara K, Wei W, Xiong Z, Arundine M, Cerwinski W . A key role for TRPM7 channels in anoxic neuronal death. Cell. 2003; 115(7):863-77. DOI: 10.1016/s0092-8674(03)01017-1. View

15.

Mattson M . Pathways towards and away from Alzheimer's disease. Nature. 2004; 430(7000):631-9. PMC: 3091392. DOI: 10.1038/nature02621. View

16.

Lacor P, Buniel M, Chang L, Fernandez S, Gong Y, Viola K . Synaptic targeting by Alzheimer's-related amyloid beta oligomers. J Neurosci. 2004; 24(45):10191-200. PMC: 6730194. DOI: 10.1523/JNEUROSCI.3432-04.2004. View

17.

Perraud A, Takanishi C, Shen B, Kang S, Smith M, Schmitz C . Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels. J Biol Chem. 2004; 280(7):6138-48. DOI: 10.1074/jbc.M411446200. View

18.

Savonenko A, Xu G, Melnikova T, Morton J, Gonzales V, Wong M . Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol Dis. 2005; 18(3):602-17. DOI: 10.1016/j.nbd.2004.10.022. View

19.

Snyder E, Nong Y, Almeida C, Paul S, Moran T, Choi E . Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005; 8(8):1051-8. DOI: 10.1038/nn1503. View

20.

Fonfria E, Marshall I, Boyfield I, Skaper S, Hughes J, Owen D . Amyloid beta-peptide(1-42) and hydrogen peroxide-induced toxicity are mediated by TRPM2 in rat primary striatal cultures. J Neurochem. 2005; 95(3):715-23. DOI: 10.1111/j.1471-4159.2005.03396.x. View