The microglial-motoneuron dialogue in ALS - PubMed (original) (raw)
Review
The microglial-motoneuron dialogue in ALS
S H Appel et al. Acta Myol. 2011 Jun.
Abstract
Neuroinflammation is a pathological hallmark of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), and is characterized by activated microglia at sites of neuronal injury. In ALS, neurons do not die alone; neuronal injury is noncell-autonomous and depends upon a well-orchestrated dialogue between motor neurons and microglia. Evidence from transgenic models expressing mutant superoxide dismutase 1 (SOD) suggests that the dialogue between motor neurons and microglia initially protects motor neurons. However, with increasing stress and injury within motor neurons, induced by the presence of misfolded proteins such as mSOD1, mitochondrial function and axoplasmic flow are impaired and endoplasmic reticulum stress is induced; misfolded proteins themselves or alternate signals are released from motor neurons and activate microglia. Activated microglia, in turn, switch from anti-inflammatory and neuroprotective to proinflammatory and neurotoxic. Neurotoxic signaling from motor neurons promotes microglial release of reactive oxygen species and pro-inflammatory cytokines further enhancing motor neuron stress and cell injury and initiating a self-propagating cycle of motor neuron injury and cell death. A greater understanding of how to restore the imbalance between neuroprotection and cytotoxicity will depend upon a greater understanding of the motor neuron-microglial dialogue.
Figures
Figure 1.
Microglia- Innate immune Cells of the CNS help mediate the balance between neuroprotection and cytotoxicity.
Figure 2.
Major themes in ALS pathogenesis.
Similar articles
- System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice.
Mesci P, Zaïdi S, Lobsiger CS, Millecamps S, Escartin C, Seilhean D, Sato H, Mallat M, Boillée S. Mesci P, et al. Brain. 2015 Jan;138(Pt 1):53-68. doi: 10.1093/brain/awu312. Epub 2014 Nov 10. Brain. 2015. PMID: 25384799 Free PMC article. - Extracellular mutant SOD1 induces microglial-mediated motoneuron injury.
Zhao W, Beers DR, Henkel JS, Zhang W, Urushitani M, Julien JP, Appel SH. Zhao W, et al. Glia. 2010 Jan 15;58(2):231-43. doi: 10.1002/glia.20919. Glia. 2010. PMID: 19672969 Free PMC article. - T cell-microglial dialogue in Parkinson's disease and amyotrophic lateral sclerosis: are we listening?
Appel SH, Beers DR, Henkel JS. Appel SH, et al. Trends Immunol. 2010 Jan;31(1):7-17. doi: 10.1016/j.it.2009.09.003. Epub 2009 Oct 31. Trends Immunol. 2010. PMID: 19879804 Free PMC article. Review. - Diphenyl diselenide protects motor neurons through inhibition of microglia-mediated inflammatory injury in amyotrophic lateral sclerosis.
Zhang C, Wang H, Liang W, Yang Y, Cong C, Wang Y, Wang S, Wang X, Wang D, Huo D, Feng H. Zhang C, et al. Pharmacol Res. 2021 Mar;165:105457. doi: 10.1016/j.phrs.2021.105457. Epub 2021 Jan 27. Pharmacol Res. 2021. PMID: 33515706 - Microglia in ALS: the good, the bad, and the resting.
Henkel JS, Beers DR, Zhao W, Appel SH. Henkel JS, et al. J Neuroimmune Pharmacol. 2009 Dec;4(4):389-98. doi: 10.1007/s11481-009-9171-5. J Neuroimmune Pharmacol. 2009. PMID: 19731042 Review.
Cited by
- Evaluation of a Synthetic Retinoid, Ellorarxine, in the NSC-34 Cell Model of Motor Neuron Disease.
Escudier O, Zhang Y, Whiting A, Chazot P. Escudier O, et al. Int J Mol Sci. 2024 Sep 10;25(18):9764. doi: 10.3390/ijms25189764. Int J Mol Sci. 2024. PMID: 39337251 Free PMC article. - Microglia-induced neuroinflammation in hippocampal neurogenesis following traumatic brain injury.
Navabi SP, Badreh F, Khombi Shooshtari M, Hajipour S, Moradi Vastegani S, Khoshnam SE. Navabi SP, et al. Heliyon. 2024 Aug 8;10(16):e35869. doi: 10.1016/j.heliyon.2024.e35869. eCollection 2024 Aug 30. Heliyon. 2024. PMID: 39220913 Free PMC article. Review. - Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer's disease.
Xiong W, Liu Y, Zhou H, Li J, Jing S, Jiang C, Li M, He Y, Ye Q. Xiong W, et al. Int J Oral Sci. 2024 May 13;16(1):40. doi: 10.1038/s41368-024-00300-4. Int J Oral Sci. 2024. PMID: 38740746 Free PMC article. - Advances of Genome Editing with CRISPR/Cas9 in Neurodegeneration: The Right Path towards Therapy.
Klinkovskij A, Shepelev M, Isaakyan Y, Aniskin D, Ulasov I. Klinkovskij A, et al. Biomedicines. 2023 Dec 17;11(12):3333. doi: 10.3390/biomedicines11123333. Biomedicines. 2023. PMID: 38137554 Free PMC article. Review. - Microglial crosstalk with astrocytes and immune cells in amyotrophic lateral sclerosis.
Calafatti M, Cocozza G, Limatola C, Garofalo S. Calafatti M, et al. Front Immunol. 2023 Jul 26;14:1223096. doi: 10.3389/fimmu.2023.1223096. eCollection 2023. Front Immunol. 2023. PMID: 37564648 Free PMC article. Review.
References
- Gurney ME, Pu H, Chiu AY, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 1994;264:1772–1775. - PubMed
- Henkel JS, Engelhardt JI, Siklos L, et al. Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol. 2004;55:221–223. - PubMed
- Henkel JS, Beers DR, Siklós L, et al. The chemokine MCP-1 and the dendritic and myeloid cells it attracts are increased in the mSOD1 mouse model of ALS. Mol Cell Neurosci. 2006;31:427–437. - PubMed
- Clement AM, Nguyen MD, Roberts EA, et al. Wild-type noneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science. 2003;302:113–117. - PubMed
- Cardona AE, Pioro EP, Sasse ME, et al. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. 2006;9:917–924. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous