Interleukin-17A in Alzheimer's Disease: Recent Advances and Controversies

Overview

Journal Curr Neuropharmacol

Publisher Bentham Science Publishers

Date 2021 Aug 25

PMID 34429057

Citations 6

Authors

Xin-Zhu Yan

Laijun Lai

Qiang Ao

Xiao-Hong Tian

Yan-Hui Zhang

Affiliations

Soon will be listed here.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease that mainly affects older adults. Although the global burden of AD is increasing year by year, the causes of AD remain largely unknown. Numerous basic and clinical studies have shown that interleukin-17A (IL-17A) may play a significant role in the pathogenesis of AD. A comprehensive assessment of the role of IL-17A in AD would benefit the diagnosis, understanding of etiology and treatment. However, over the past decade, controversies remain regarding the expression level and role of IL-17A in AD. We have incorporated newly published researches and point out that IL-17A expression levels may vary along with the development of AD, exercising different roles at different stages of AD, although much more work remains to be done to support the potential role of IL-17A in AD-related pathology. Here, it is our intention to review the underlying mechanisms of IL-17A in AD and address the current controversies in an effort to clarify the results of existing research and suggest future studies.

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References

Ni P, Dong H, Wang Y, Zhou Q, Xu M, Qian Y . IL-17A contributes to perioperative neurocognitive disorders through blood-brain barrier disruption in aged mice. J Neuroinflammation. 2018; 15(1):332. PMC: 6267879. DOI: 10.1186/s12974-018-1374-3. View

Varvel N, Neher J, Bosch A, Wang W, Ransohoff R, Miller R . Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus. Proc Natl Acad Sci U S A. 2016; 113(38):E5665-74. PMC: 5035862. DOI: 10.1073/pnas.1604263113. View

Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M . Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 2007; 13(10):1173-5. PMC: 5114125. DOI: 10.1038/nm1651. View

Cua D, Tato C . Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010; 10(7):479-89. DOI: 10.1038/nri2800. View

Sun J, Zhang S, Zhang X, Zhang X, Dong H, Qian Y . IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. J Neuroinflammation. 2015; 12:165. PMC: 4572693. DOI: 10.1186/s12974-015-0394-5. View

Satoh J, Tabunoki H, Ishida T, Saito Y, Arima K . Accumulation of a repulsive axonal guidance molecule RGMa in amyloid plaques: a possible hallmark of regenerative failure in Alzheimer's disease brains. Neuropathol Appl Neurobiol. 2012; 39(2):109-20. DOI: 10.1111/j.1365-2990.2012.01281.x. View

Zhou Y, Chen Y, Xu C, Zhang H, Lin C . TLR4 Targeting as a Promising Therapeutic Strategy for Alzheimer Disease Treatment. Front Neurosci. 2021; 14:602508. PMC: 7775514. DOI: 10.3389/fnins.2020.602508. View

Lim M, Lee J, Park J, Jhun J, Moon Y, Cho M . Increased Th17 differentiation in aged mice is significantly associated with high IL-1β level and low IL-2 expression. Exp Gerontol. 2013; 49:55-62. DOI: 10.1016/j.exger.2013.10.006. View

Liu Q, Xin W, He P, Turner D, Yin J, Gan Y . Interleukin-17 inhibits adult hippocampal neurogenesis. Sci Rep. 2014; 4:7554. PMC: 4271266. DOI: 10.1038/srep07554. View

10.

Tanabe S, Yamashita T . Repulsive guidance molecule-a is involved in Th17-cell-induced neurodegeneration in autoimmune encephalomyelitis. Cell Rep. 2014; 9(4):1459-70. DOI: 10.1016/j.celrep.2014.10.038. View

11.

Terry R, Masliah E, Salmon D, Butters N, DeTeresa R, Hill R . Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991; 30(4):572-80. DOI: 10.1002/ana.410300410. View

12.

Oberstein T, Taha L, Spitzer P, Hellstern J, Herrmann M, Kornhuber J . Imbalance of Circulating T17 and Regulatory T Cells in Alzheimer's Disease: A Case Control Study. Front Immunol. 2018; 9:1213. PMC: 5994416. DOI: 10.3389/fimmu.2018.01213. View

13.

Gao L, Li P, Shao T, Mao X, Qi H, Wu B . Neurotoxic role of interleukin-17 in neural stem cell differentiation after intracerebral hemorrhage. Neural Regen Res. 2020; 15(7):1350-1359. PMC: 7047805. DOI: 10.4103/1673-5374.272614. View

14.

van de Haar H, Burgmans S, Jansen J, van Osch M, van Buchem M, Muller M . Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease. Radiology. 2017; 282(2):615. DOI: 10.1148/radiol.2017164043. View

15.

Doecke J, Laws S, Faux N, Wilson W, Burnham S, Lam C . Blood-based protein biomarkers for diagnosis of Alzheimer disease. Arch Neurol. 2012; 69(10):1318-25. PMC: 6287606. DOI: 10.1001/archneurol.2012.1282. View

16.

Selkoe D . Alzheimer's disease is a synaptic failure. Science. 2002; 298(5594):789-91. DOI: 10.1126/science.1074069. View

17.

Zenaro E, Pietronigro E, Della Bianca V, Piacentino G, Marongiu L, Budui S . Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin. Nat Med. 2015; 21(8):880-6. DOI: 10.1038/nm.3913. View

18.

Yang J, Kou J, Lalonde R, Fukuchi K . Intracranial IL-17A overexpression decreases cerebral amyloid angiopathy by upregulation of ABCA1 in an animal model of Alzheimer's disease. Brain Behav Immun. 2017; 65:262-273. PMC: 5537015. DOI: 10.1016/j.bbi.2017.05.012. View

19.

Hodson R . Alzheimer's disease. Nature. 2018; 559(7715):S1. DOI: 10.1038/d41586-018-05717-6. View

20.

Yang Z, Yuan C . IL-17A promotes the neuroinflammation and cognitive function in sevoflurane anesthetized aged rats via activation of NF-κB signaling pathway. BMC Anesthesiol. 2018; 18(1):147. PMC: 6195755. DOI: 10.1186/s12871-018-0607-4. View