Microglia and neuroprotection: from in vitro studies to therapeutic applications - PubMed (original) (raw)
Review
Microglia and neuroprotection: from in vitro studies to therapeutic applications
Elisabetta Polazzi et al. Prog Neurobiol. 2010 Nov.
Abstract
Microglia are the main immune cells in the brain, playing a role in both physiological and pathological conditions. Microglial involvement in neurodegenerative diseases is well-established, being microglial activation and neuroinflammation common features of these neuropathologies. Microglial activation has been considered harmful for neurons, but inflammatory state is not only associated with neurotoxic consequences, but also with neuroprotective effects, such as phagocytosis of dead neurons and clearance of debris. This brought to the idea of protective autoimmunity in the brain and to devise immunomodulatory therapies, aimed to specifically increase neuroprotective aspects of microglia. During the last years, several data supported the intrinsic neuroprotective function of microglia through the release of neuroprotective molecules. These data led to change the traditional view of microglia in neurodegenerative diseases: from the idea that these cells play an detrimental role for neurons due to a gain of their inflammatory function, to the proposal of a loss of microglial neuroprotective function as a causing factor in neuropathologies. This "microglial dysfunction hypothesis" points at the importance of understanding the mechanisms of microglial-mediated neuroprotection to develop new therapies for neurodegenerative diseases. In vitro models are very important to clarify the basic mechanisms of microglial-mediated neuroprotection, mainly for the identification of potentially effective neuroprotective molecules, and to design new approaches in a gene therapy set-up. Microglia could act as both a target and a vehicle for CNS gene delivery of neuroprotective factors, endogenously produced by microglia in physiological conditions, thus strengthening the microglial neuroprotective phenotype, even in a pathological situation.
Copyright © 2010 Elsevier Ltd. All rights reserved.
Similar articles
- Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation.
Liu Y, Qin L, Li G, Zhang W, An L, Liu B, Hong JS. Liu Y, et al. J Pharmacol Exp Ther. 2003 Apr;305(1):212-8. doi: 10.1124/jpet.102.043166. J Pharmacol Exp Ther. 2003. PMID: 12649371 - Microglial activation in chronic neurodegenerative diseases: roles of apoptotic neurons and chronic stimulation.
Minghetti L, Ajmone-Cat MA, De Berardinis MA, De Simone R. Minghetti L, et al. Brain Res Brain Res Rev. 2005 Apr;48(2):251-6. doi: 10.1016/j.brainresrev.2004.12.015. Epub 2005 Jan 18. Brain Res Brain Res Rev. 2005. PMID: 15850664 Review. - Neuronal injury in chronic CNS inflammation.
Zindler E, Zipp F. Zindler E, et al. Best Pract Res Clin Anaesthesiol. 2010 Dec;24(4):551-62. doi: 10.1016/j.bpa.2010.11.001. Epub 2010 Nov 29. Best Pract Res Clin Anaesthesiol. 2010. PMID: 21619866 Review. - Catalpol protects dopaminergic neurons from LPS-induced neurotoxicity in mesencephalic neuron-glia cultures.
Tian YY, An LJ, Jiang L, Duan YL, Chen J, Jiang B. Tian YY, et al. Life Sci. 2006 Dec 23;80(3):193-9. doi: 10.1016/j.lfs.2006.09.010. Epub 2006 Sep 20. Life Sci. 2006. PMID: 17049947 - Microglia and neuroprotection: implications for Alzheimer's disease.
Streit WJ. Streit WJ. Brain Res Brain Res Rev. 2005 Apr;48(2):234-9. doi: 10.1016/j.brainresrev.2004.12.013. Epub 2005 Jan 15. Brain Res Brain Res Rev. 2005. PMID: 15850662 Review.
Cited by
- Early prediction of putamen imaging features in HIV-associated neurocognitive impairment syndrome.
Qi Y, Xu M, Wang W, Wang YY, Liu JJ, Ren HX, Liu MM, Li RL, Li HJ. Qi Y, et al. BMC Neurol. 2021 Mar 9;21(1):106. doi: 10.1186/s12883-021-02114-x. BMC Neurol. 2021. PMID: 33750319 Free PMC article. - Microglial HIV-1 Expression: Role in HIV-1 Associated Neurocognitive Disorders.
Li H, McLaurin KA, Illenberger JM, Mactutus CF, Booze RM. Li H, et al. Viruses. 2021 May 17;13(5):924. doi: 10.3390/v13050924. Viruses. 2021. PMID: 34067600 Free PMC article. - WKYMVm/FPR2 Alleviates Spinal Cord Injury by Attenuating the Inflammatory Response of Microglia.
Zhang W, Chen J, Guo W, Kong G, Wang L, Cheng X, Zeng X, Wan Y, Li X. Zhang W, et al. Mediators Inflamm. 2022 Jul 27;2022:4408099. doi: 10.1155/2022/4408099. eCollection 2022. Mediators Inflamm. 2022. PMID: 35935810 Free PMC article. - Wnt family member 1 (Wnt1) overexpression-induced M2 polarization of microglia alleviates inflammation-sensitized neonatal brain injuries.
Gao J, Xu H, Rong Z, Chen L. Gao J, et al. Bioengineered. 2022 May;13(5):12409-12420. doi: 10.1080/21655979.2022.2074767. Bioengineered. 2022. PMID: 35603707 Free PMC article. - Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation.
Ye X, Zhu M, Che X, Wang H, Liang XJ, Wu C, Xue X, Yang J. Ye X, et al. J Neuroinflammation. 2020 Jan 11;17(1):18. doi: 10.1186/s12974-019-1644-8. J Neuroinflammation. 2020. PMID: 31926553 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources