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Acquired neuroprotection is a synaptic-activity-dependent form of adaptation in the nervous system that renders neurons more resistant to harmful conditions. The term was coined by Hilmar Bading. This use-dependent enhancement of cellular survival activity requires changes in gene expression triggered by neuronal activity and nuclear calcium signaling. In rodents, components of the neuroprotective gene program can reduce brain damage caused by seizure-like activity or by a stroke. In acute and chronic neurodegenerative diseases, gene regulatory events important for acquired neuroprotection are antagonized by extrasynaptic NMDA receptor signaling leading to increased vulnerability, loss of structural integrity, and bioenergetics dysfunction.
References
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- ↑ Petralia, R. S.; Wang, Y. X.; Hua, F.; Yi, Z.; Zhou, A.; Ge, L.; Stephenson, F. A.; Wenthold, R. J. (2010-04-28). "Organization of NMDA receptors at extrasynaptic locations". Neuroscience. 167 (1): 68–87. doi:10.1016/j.neuroscience.2010.01.022. ISSN 1873-7544. PMC 2840201 . PMID 20096331.
- ↑ Hardingham, G. E.; Fukunaga, Y.; Bading, H. (2002-05-01). "Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways". Nature Neuroscience. 5 (5): 405–414. doi:10.1038/nn835. ISSN 1097-6256. PMID 11953750. S2CID 659716.
- ↑ Okamoto, Shu-ichi; Pouladi, Mahmoud A.; Talantova, Maria; Yao, Dongdong; Xia, Peng; Ehrnhoefer, Dagmar E.; Zaidi, Rameez; Clemente, Arjay; Kaul, Marcus (2009-12-01). "Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin". Nature Medicine. 15 (12): 1407–1413. doi:10.1038/nm.2056. ISSN 1546-170X. PMC 2789858 . PMID 19915593.
- ↑ Milnerwood, Austen J.; Gladding, Clare M.; Pouladi, Mahmoud A.; Kaufman, Alexandra M.; Hines, Rochelle M.; Boyd, Jamie D.; Ko, Rebecca W. Y.; Vasuta, Oana C.; Graham, Rona K. (2010-01-28). "Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice". Neuron. 65 (2): 178–190. doi: 10.1016/j.neuron.2010.01.008 . ISSN 1097-4199. PMID 20152125.
- ↑ Talantova, Maria; Sanz-Blasco, Sara; Zhang, Xiaofei; Xia, Peng; Akhtar, Mohd Waseem; Okamoto, Shu-ichi; Dziewczapolski, Gustavo; Nakamura, Tomohiro; Cao, Gang (2013-07-02). "Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss". Proceedings of the National Academy of Sciences of the United States of America. 110 (27): E2518–2527. Bibcode:2013PNAS..110E2518T. doi: 10.1073/pnas.1306832110 . ISSN 1091-6490. PMC 3704025 . PMID 23776240.
- ↑ Hardingham, Giles E.; Bading, Hilmar (2010-10-01). "Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders". Nature Reviews. Neuroscience. 11 (10): 682–696. doi:10.1038/nrn2911. ISSN 1471-0048. PMC 2948541 . PMID 20842175.
- ↑ Parsons, Matthew P.; Raymond, Lynn A. (2014-04-16). "Extrasynaptic NMDA receptor involvement in central nervous system disorders". Neuron. 82 (2): 279–293. doi: 10.1016/j.neuron.2014.03.030 . ISSN 1097-4199. PMID 24742457.
- ↑ Yan, Jing; Bengtson, C. Peter; Buchthal, Bettina; Hagenston, Anna M.; Bading, Hilmar (9 October 2020). "Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants". Science. 370 (6513): eaay3302. doi:10.1126/science.aay3302. ISSN 1095-9203. PMID 33033186. S2CID 222210921.
- ↑ Yan, Jing; Bengtson, C. Peter; Buchthal, Bettina; Hagenston, Anna M.; Bading, Hilmar (9 October 2020). "Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants". Science. 370 (6513): eaay3302. doi:10.1126/science.aay3302. ISSN 1095-9203. PMID 33033186. S2CID 222210921.
- ↑ "New Class of Highly Effective Inhibitors Protects against Neurodegeneration – Heidelberg University". www.uni-heidelberg.de. Retrieved 2020-10-29.