Neuroinflammation and Neurogenesis in Alzheimer's Disease and Potential Therapeutic Approaches

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Jan 25

PMID 31973106

Citations 79

Authors

Pi-Shan Sung

Po-Yu Lin

Chi-Hung Liu

Hui-Chen Su

Kuen-Jer Tsai

Affiliations

Soon will be listed here.

Abstract

In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer's disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

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References

Ermini F, Grathwohl S, Radde R, Yamaguchi M, Staufenbiel M, Palmer T . Neurogenesis and alterations of neural stem cells in mouse models of cerebral amyloidosis. Am J Pathol. 2008; 172(6):1520-8. PMC: 2408413. DOI: 10.2353/ajpath.2008.060520. View

Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P . What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer's disease, about the therapeutic strategies in Alzheimer's research. J Neural Transm (Vienna). 2012; 120(1):233-52. DOI: 10.1007/s00702-012-0877-9. View

Marxreiter F, Regensburger M, Winkler J . Adult neurogenesis in Parkinson's disease. Cell Mol Life Sci. 2012; 70(3):459-73. PMC: 11113680. DOI: 10.1007/s00018-012-1062-x. View

Wittko I, Schanzer A, Kuzmichev A, Schneider F, Shibuya M, Raab S . VEGFR-1 regulates adult olfactory bulb neurogenesis and migration of neural progenitors in the rostral migratory stream in vivo. J Neurosci. 2009; 29(27):8704-14. PMC: 3865485. DOI: 10.1523/JNEUROSCI.5527-08.2009. View

Li B, Yamamori H, Tatebayashi Y, Shafit-Zagardo B, Tanimukai H, Chen S . Failure of neuronal maturation in Alzheimer disease dentate gyrus. J Neuropathol Exp Neurol. 2007; 67(1):78-84. PMC: 3191920. DOI: 10.1097/nen.0b013e318160c5db. View

Lee C, Landreth G . The role of microglia in amyloid clearance from the AD brain. J Neural Transm (Vienna). 2010; 117(8):949-60. PMC: 3653296. DOI: 10.1007/s00702-010-0433-4. View

Louissaint Jr A, Rao S, Leventhal C, Goldman S . Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain. Neuron. 2002; 34(6):945-60. DOI: 10.1016/s0896-6273(02)00722-5. View

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

Terwel D, Steffensen K, Verghese P, Kummer M, Gustafsson J, Holtzman D . Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis. J Neurosci. 2011; 31(19):7049-59. PMC: 6703224. DOI: 10.1523/JNEUROSCI.6546-10.2011. View

10.

Sun C, Chuang H, Wang J, Chen S, Cheng Y, Lee C . The A2A adenosine receptor rescues neuritogenesis impaired by p53 blockage via KIF2A, a kinesin family member. Dev Neurobiol. 2010; 70(8):604-21. DOI: 10.1002/dneu.20802. View

11.

Yuan H, Chen R, Wu L, Chen Q, Hu A, Zhang T . The regulatory mechanism of neurogenesis by IGF-1 in adult mice. Mol Neurobiol. 2014; 51(2):512-22. DOI: 10.1007/s12035-014-8717-6. View

12.

Sun G, Yu R, Evans R, Shi Y . Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc Natl Acad Sci U S A. 2007; 104(39):15282-7. PMC: 2000559. DOI: 10.1073/pnas.0704089104. View

13.

Maruszak A, Pilarski A, Murphy T, Branch N, Thuret S . Hippocampal neurogenesis in Alzheimer's disease: is there a role for dietary modulation?. J Alzheimers Dis. 2013; 38(1):11-38. DOI: 10.3233/JAD-131004. View

14.

Halliday G, Robinson S, Shepherd C, Kril J . Alzheimer's disease and inflammation: a review of cellular and therapeutic mechanisms. Clin Exp Pharmacol Physiol. 2000; 27(1-2):1-8. DOI: 10.1046/j.1440-1681.2000.03200.x. View

15.

Liao Y, Wang B, Cheng H, Kuo L, Wolfe M . Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem. 2004; 279(47):49523-32. DOI: 10.1074/jbc.M402034200. View

16.

Sudduth T, Schmitt F, Nelson P, Wilcock D . Neuroinflammatory phenotype in early Alzheimer's disease. Neurobiol Aging. 2012; 34(4):1051-9. PMC: 3579221. DOI: 10.1016/j.neurobiolaging.2012.09.012. View

17.

Belarbi K, Burnouf S, Fernandez-Gomez F, Laurent C, Lestavel S, Figeac M . Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology. Neurobiol Dis. 2011; 43(2):486-94. DOI: 10.1016/j.nbd.2011.04.022. View

18.

Boekhoorn K, Joels M, Lucassen P . Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus. Neurobiol Dis. 2006; 24(1):1-14. DOI: 10.1016/j.nbd.2006.04.017. View

19.

Horgusluoglu E, Nudelman K, Nho K, Saykin A . Adult neurogenesis and neurodegenerative diseases: A systems biology perspective. Am J Med Genet B Neuropsychiatr Genet. 2016; 174(1):93-112. PMC: 4987273. DOI: 10.1002/ajmg.b.32429. View

20.

Paolicelli R, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P . Synaptic pruning by microglia is necessary for normal brain development. Science. 2011; 333(6048):1456-8. DOI: 10.1126/science.1202529. View