The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Nerve growth factor (NGF) and pro‐NGF increase low‐density lipoprotein (LDL) receptors in neuronal cells partly by different mechanisms: role of LDL in neurite outgrowth
Abstract
Low‐density lipoprotein receptors (LDLR s) mediate the uptake of lipoprotein particles into cells, as studied mainly in peripheral tissues. Here, we show that nerve growth factor (NGF) increases LDLR levels in PC 6.3 cells and in cultured septal neurons from embryonic rat brain. Study of the mechanisms showed that NGF enhanced transcription of the LDLR gene, acting mainly via Tropomyosin receptor kinase A receptors. Simvastatin, a cholesterol‐lowering drug, also increased the LDLR expression in PC 6.3 cells. In addition, pro‐NGF and pro‐brain‐derived neurotrophic factor, acting via the p75 neurotrophin receptor (p75 NTR) also increased LDLR s. We further observed that Myosin Regulatory Light Chain‐Interacting Protein/Inducible Degrader of the LDLR (Mylip/Idol) was down‐regulated by pro‐NGF, whereas the other LDLR regulator, proprotein convertase subtilisin kexin 9 (PCSK 9) was not significantly changed. On the functional side, NGF and pro‐NGF increased lipoprotein uptake by neuronal cells as shown using diacetyl‐labeled LDL. The addition of serum‐derived lipoprotein particles in conjunction with NGF or simvastatin enhanced neurite outgrowth. Collectively, these results show that NGF and simvastatin are able to stimulate lipoprotein uptake by neurons with a positive effect on neurite outgrowth. Increases in LDLR s and lipoprotein particles in neurons could play a functional role during brain development, in neuroregeneration and after brain injuries. image Nerve growth factor (NGF) and pro‐NGF induce the expression of low‐density lipoprotein receptors (LDLRs) in neuronal cells leading to increased LDLR levels. Pro‐NGF also down‐regulated myosin regulatory light chain‐interacting protein/inducible degrader of the LDLR (Mylip/Idol) that is involved in the degradation of LDLRs. NGF acts mainly via Tropomyosin receptor kinase A (TrkA) receptors, whereas pro‐NGF stimulates p75 neurotrophin receptor (p75NTR). Elevated LDLRs upon NGF and pro‐NGF treatments enhanced lipoprotein uptake by neurons. Addition of LDL particles further led to the stimulation of neurite outgrowth in PC6.3 cells after NGF or simvastatin treatments, suggesting a stimulatory role of lipoproteins on neuronal differentiation. In contrast, pro‐NGF had no effect on neurite outgrowth either in the absence or presence of LDL particles. The precise mechanisms by which increased lipoproteins uptake can affect neurite outgrowth warrant further studies.
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Metadata
- Authors
- Do, H. T., Bruelle, C., Pham, D. D., Jauhiainen, M., Eriksson, O., Korhonen, L. T., & Lindholm, D.
- Affiliations
- Department of Biochemistry and Developmental Biology Medical Faculty Medicum University of Helsinki Helsinki Finland
- University of Helsinki (FI)
- Finnish Institute for Health and Welfare (FI)
- Minerva Foundation (FI)
- Corresponding author
- Lindholm, Dan
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2015-11-19
- Volume
- 136
- Issue
- 2
- Pages
- 306-315
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1771341671
- Semantic Scholar
- 4e92a0ff79faf1516f94edb223a1c288762d9f95
- Cited by
- 37
- References
- 43
- Citations by year
- 2025: 6 · 2023: 6 · 2022: 6 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 1
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- Magnus Ehrnroothin Säätiö
- Parkinsonfonden
- Minerva Foundation
- Sigrid Juséliuksen Säätiö
- Suomen Akatemia
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- nerve growth factor, LDL receptor, TrkA, p75 neurotrophin receptor, simvastatin, PCSK9, lipoprotein uptake, neurite outgrowth, septal neurons, nerve regeneration, brain injury, brain development
- MeSH terms
- Animals, Antibodies, Benzoates, Benzylamines, Carbazoles, Cells, Cultured, Embryo, Mammalian, Enzyme Inhibitors, Gene Expression Regulation, Humans, Lipoproteins, LDL, Nerve Growth Factors, Neurons, Protein Precursors, Receptors, LDL, Neurites, Culture Media, Serum-Free, Rats, Wistar, Receptors, Nerve Growth Factor, Simvastatin, Septum of Brain, Nerve Growth Factor, Indole Alkaloids, Rats
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