Neurotrophins As Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jun 2

PMID 34073639

Citations 17

Authors

Mayra Colardo

Noemi Martella

Daniele Pensabene

Silvia Siteni

Sabrina Di Bartolomeo

Valentina Pallottini

Marco Segatto

Affiliations

Soon will be listed here.

Abstract

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins' signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.

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References

Yuan W, Ibanez C, Lin Z . Death domain of p75 neurotrophin receptor: a structural perspective on an intracellular signalling hub. Biol Rev Camb Philos Soc. 2019; 94(4):1282-1293. DOI: 10.1111/brv.12502. View

Li R, Wu Y, Zou S, Wang X, Li Y, Xu K . NGF Attenuates High Glucose-Induced ER Stress, Preventing Schwann Cell Apoptosis by Activating the PI3K/Akt/GSK3β and ERK1/2 Pathways. Neurochem Res. 2017; 42(11):3005-3018. DOI: 10.1007/s11064-017-2333-6. View

Sharma E, Behl T, Mehta V, Kumar A, Setia D, Uddin M . Exploring the Various Aspects of Brain-Derived Neurotropic Factor (BDNF) in Diabetes Mellitus. CNS Neurol Disord Drug Targets. 2020; 20(1):22-33. DOI: 10.2174/1871527319666201014125642. View

Houtz J, Borden P, Ceasrine A, Minichiello L, Kuruvilla R . Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion. Dev Cell. 2016; 39(3):329-345. PMC: 5123838. DOI: 10.1016/j.devcel.2016.10.003. View

Luo J, Yang H, Song B . Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol Cell Biol. 2019; 21(4):225-245. DOI: 10.1038/s41580-019-0190-7. View

Lee Y, Lee H, Lee S, Min D, Baek S, Kim Y . Down-regulation of phospholipase C-gamma 1 during the differentiation of U937 cells. FEBS Lett. 1995; 358(2):105-8. DOI: 10.1016/0014-5793(94)01404-o. View

Block R, Ray Dorsey E, Beck C, Brenna J, Shoulson I . Altered cholesterol and fatty acid metabolism in Huntington disease. J Clin Lipidol. 2010; 4(1):17-23. PMC: 2926984. DOI: 10.1016/j.jacl.2009.11.003. View

Jin W . Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson's Disease. J Clin Med. 2020; 9(1). PMC: 7019526. DOI: 10.3390/jcm9010257. View

Maisonpierre P, Belluscio L, Squinto S, Ip N, Furth M, Lindsay R . Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990; 247(4949 Pt 1):1446-51. DOI: 10.1126/science.247.4949.1446. View

10.

Joyce C, Shelness G, Davis M, Lee R, Skinner K, Anderson R . ACAT1 and ACAT2 membrane topology segregates a serine residue essential for activity to opposite sides of the endoplasmic reticulum membrane. Mol Biol Cell. 2000; 11(11):3675-87. PMC: 15029. DOI: 10.1091/mbc.11.11.3675. View

11.

Engel D, Grzyb A, de Oliveira J, Potzsch A, Walker T, Brocardo P . Impaired adult hippocampal neurogenesis in a mouse model of familial hypercholesterolemia: A role for the LDL receptor and cholesterol metabolism in adult neural precursor cells. Mol Metab. 2019; 30:1-15. PMC: 6812372. DOI: 10.1016/j.molmet.2019.09.002. View

12.

Rudenko G, Henry L, Henderson K, Ichtchenko K, Brown M, Goldstein J . Structure of the LDL receptor extracellular domain at endosomal pH. Science. 2002; 298(5602):2353-8. DOI: 10.1126/science.1078124. View

13.

Levi-Montalcini R . From Turin to Stockholm via St. Louis and Rio de Janeiro. Science. 2000; 287(5454):809. DOI: 10.1126/science.287.5454.809. View

14.

Moon S, Huang C, Houlihan S, Regunath K, Freed-Pastor W, Morris 4th J . p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression. Cell. 2018; 176(3):564-580.e19. PMC: 6483089. DOI: 10.1016/j.cell.2018.11.011. View

15.

Garcia C, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M . Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. 2001; 292(5520):1394-8. DOI: 10.1126/science.1060458. View

16.

Grana T, LaMarre J, Kalisch B . Nerve growth factor-mediated regulation of low density lipoprotein receptor-related protein promoter activation. Cell Mol Neurobiol. 2012; 33(2):269-82. PMC: 11497883. DOI: 10.1007/s10571-012-9894-3. View

17.

Paolo G, Kim T . Linking lipids to Alzheimer's disease: cholesterol and beyond. Nat Rev Neurosci. 2011; 12(5):284-96. PMC: 3321383. DOI: 10.1038/nrn3012. View

18.

Chu B, Ge L, Xie C, Zhao Y, Miao H, Wang J . Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. J Biol Chem. 2009; 284(33):22481-22490. PMC: 2755969. DOI: 10.1074/jbc.M109.034355. View

19.

Vanier M, Millat G . Niemann-Pick disease type C. Clin Genet. 2003; 64(4):269-81. DOI: 10.1034/j.1399-0004.2003.00147.x. View

20.

Lessmann V, Gottmann K, Malcangio M . Neurotrophin secretion: current facts and future prospects. Prog Neurobiol. 2003; 69(5):341-74. DOI: 10.1016/s0301-0082(03)00019-4. View