FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins

Mirolyuba Ilieva; Troels T. Nielsen; Tanja Michel; Stanislava Pankratova

doi:10.1007/s00702-019-02073-1

FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins

Mirolyuba Ilieva, Troels T. Nielsen, Tanja Michel, Stanislava Pankratova

Abstract

In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt–related effects on neuronal placticity.

Original language	English
Journal	Journal of Neural Transmission
Volume	126
Issue number	11
Pages (from-to)	1493-1500
Number of pages	8
ISSN	0300-9564
DOIs	https://doi.org/10.1007/s00702-019-02073-1
Publication status	Published - 1 Nov 2019

Keywords

Huntington disease
Mutant huntingtin
FGF2
Enreptin
Neurite outgrowth
Hippocampal neurons

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10.1007/s00702-019-02073-1

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FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins. / Ilieva, Mirolyuba; Nielsen, Troels T.; Michel, Tanja et al.

In: Journal of Neural Transmission, Vol. 126, No. 11, 01.11.2019, p. 1493-1500.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins",

abstract = "In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt–related effects on neuronal placticity.",

keywords = "Huntington disease, Mutant huntingtin, FGF2, Enreptin, Neurite outgrowth, Hippocampal neurons",

author = "Mirolyuba Ilieva and Nielsen, {Troels T.} and Tanja Michel and Stanislava Pankratova",

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AU - Michel, Tanja

AU - Pankratova, Stanislava

PY - 2019/11/1

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N2 - In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt–related effects on neuronal placticity.

AB - In the present study, we developed an in vitro model of Huntington disease (HD) by transfecting primary rat hippocampal neurons with plasmids coding for m-htt exon 1 with different number of CAG repeats (18, 50 and 115) and demonstrated the influence of the length of polyQ sequence on neurite elongation. We found that exogenously applied FGF2 significantly rescued the m-htt-induced loss of neurite outgrowth. Moreover, the Enreptin peptide, an FGFR1 and NCAM dual agonist, had a similar neuritogenic effect to FGF2 in clinically relevant m-htt 50Q-expressing neurons. This study has developed an in vitro model of primary hippocampal neurons transfected with m-htt-coding vectors that is a powerful tool to study m-htt–related effects on neuronal placticity.

KW - Huntington disease

KW - Mutant huntingtin

KW - FGF2

KW - Enreptin

KW - Neurite outgrowth

KW - Hippocampal neurons

U2 - 10.1007/s00702-019-02073-1

DO - 10.1007/s00702-019-02073-1

M3 - Journal article

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SN - 0375-9245

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SP - 1493

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JO - Acta Neurovegetativa

JF - Acta Neurovegetativa

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ER -

FGF2 and dual agonist of NCAM and FGF receptor 1, Enreptin, rescue neurite outgrowth loss in hippocampal neurons expressing mutated huntingtin proteins

Abstract

Keywords

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