TLQP-62
| VGF nerve growth factor inducible | |
|---|---|
| Identifiers | |
| Symbol | VGF |
| Entrez | 7425 |
| HUGO | 12684 |
| OMIM | 602186 |
| RefSeq | NM_003378 |
| UniProt | O15240 |
| Other data | |
| Locus | Chr. 7 q22 |
TLQP-62 (amino acid 556-617) is a VGF-derived C-terminal peptide that was first discovered by Trani et al.[1] TLQP-62 is derived from VGF precursor protein via proteolytic cleavage by prohormone convertases PC1/3 at the RPR555 site.[2] TLQP-62 is named after its first four N-terminal amino acids and its peptide length.
Function
Although the receptor(s) for TLQP-62 has not been identified so far, extensive studies have demonstrated that it acts on central nervous system, peripheral nervous system and endocrine tissue to exert its biological functions.
Synaptic plasticity
Acute TLQP-62 treatment rapidly increases synaptic activity in hippocampal neurons,[3] and potentiates CA1 field excitatory postsynaptic potential fEPSP in the hippocampal slices,[4] thus facilitating hippocampal synaptic transmission. TLQP-62 also increases dendritic branching and length in cultured hippocampal neurons.[5]
Neurogenesis
TLQP-62 treatment enhances hippocampal neurogenesis both in vitro and in vivo[6] by promoting the proliferation in neuronal progenitor cells.[7]
Antidepressant efficacy
Intrahippocampal TLQP-62 infusion produces both rapid and sustained antidepressant-like effects in the forced swim test.[8][9] TLQP-62's processed peptide AQEE-30, when given via intracerebroventricular route, also elicits antidepressant-like effects.[10]
Memory and learning
Acute intrahippocampal TLQP-62 infusion enhances memory formation via BDNF/TrkB signaling.[11]
Pain
Acute intrathecal administration of TLQP-62 induces hypersensitivity to mechanical and cold stimuli that recapitulates neuropathic pain, potentially by regulating the excitability of dorsal horn neurons.[12]
Insulin secretion
TLQP-62 treatment increases insulin secretion in cultured insulinoma cells by increasing intracellular calcium mobilization.[13]
References
- ↑ Trani E, Ciotti T, Rinaldi AM, Canu N, Ferri GL, Levi A, Possenti R (December 1995). "Tissue-specific processing of the neuroendocrine protein VGF". Journal of Neurochemistry. 65 (6): 2441–9. doi:10.1046/j.1471-4159.1995.65062441.x. PMID 7595538.
- ↑ Trani E, Giorgi A, Canu N, Amadoro G, Rinaldi AM, Halban PA, Ferri GL, Possenti R, Schininà ME, Levi A (May 2002). "Isolation and characterization of VGF peptides in rat brain. Role of PC1/3 and PC2 in the maturation of VGF precursor". Journal of Neurochemistry. 81 (3): 565–74. doi:10.1046/j.1471-4159.2002.00842.x. PMID 12065665.
- ↑ Alder J, Thakker-Varia S, Bangasser DA, Kuroiwa M, Plummer MR, Shors TJ, Black IB (November 2003). "Brain-derived neurotrophic factor-induced gene expression reveals novel actions of VGF in hippocampal synaptic plasticity" (PDF). The Journal of Neuroscience. 23 (34): 10800–8. PMC 3374594. PMID 14645472.
- ↑ Bozdagi O, Rich E, Tronel S, Sadahiro M, Patterson K, Shapiro ML, Alberini CM, Huntley GW, Salton SR (September 2008). "The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism". The Journal of Neuroscience. 28 (39): 9857–69. doi:10.1523/jneurosci.3145-08.2008. PMC 2820295. PMID 18815270.
- ↑ Behnke J, Cheedalla A, Bhatt V, Bhat M, Teng S, Palmieri A, Windon CC, Thakker-Varia S, Alder J (March 2017). "Neuropeptide VGF Promotes Maturation of Hippocampal Dendrites That Is Reduced by Single Nucleotide Polymorphisms". International Journal of Molecular Sciences. 18 (3): 612. doi:10.3390/ijms18030612. PMID 28287464.
- ↑ Thakker-Varia S, Krol JJ, Nettleton J, Bilimoria PM, Bangasser DA, Shors TJ, Black IB, Alder J (November 2007). "The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus". The Journal of Neuroscience. 27 (45): 12156–67. doi:10.1523/JNEUROSCI.1898-07.2007. PMID 17989282.
- ↑ Thakker-Varia S, Behnke J, Doobin D, Dalal V, Thakkar K, Khadim F, Wilson E, Palmieri A, Antila H, Rantamaki T, Alder J (May 2014). "VGF (TLQP-62)-induced neurogenesis targets early phase neural progenitor cells in the adult hippocampus and requires glutamate and BDNF signaling". Stem Cell Research. 12 (3): 762–77. doi:10.1016/j.scr.2014.03.005. PMID 24747217.
- ↑ Thakker-Varia S, Krol JJ, Nettleton J, Bilimoria PM, Bangasser DA, Shors TJ, Black IB, Alder J (November 2007). "The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus". The Journal of Neuroscience. 27 (45): 12156–67. doi:10.1523/jneurosci.1898-07.2007. PMID 17989282.
- ↑ Jiang C, Lin WJ, Sadahiro M, Labonté B, Menard C, Pfau ML, Tamminga CA, Turecki G, Nestler EJ, Russo SJ, Salton SR (November 2017). "VGF function in depression and antidepressant efficacy". Molecular Psychiatry. doi:10.1038/mp.2017.233. PMID 29158577.
- ↑ Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS (December 2007). "Antidepressant actions of the exercise-regulated gene VGF". Nature Medicine. 13 (12): 1476–82. doi:10.1038/nm1669. PMID 18059283.
- ↑ Lin WJ, Jiang C, Sadahiro M, Bozdagi O, Vulchanova L, Alberini CM, Salton SR (July 2015). "VGF and Its C-Terminal Peptide TLQP-62 Regulate Memory Formation in Hippocampus via a BDNF-TrkB-Dependent Mechanism". The Journal of Neuroscience. 35 (28): 10343–56. doi:10.1523/JNEUROSCI.0584-15.2015. PMC 4502270. PMID 26180209.
- ↑ Moss A, Ingram R, Koch S, Theodorou A, Low L, Baccei M, Hathway GJ, Costigan M, Salton SR, Fitzgerald M (December 2008). "Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury". Molecular Pain. 4: 62. doi:10.1186/1744-8069-4-62. PMID 19077191.
- ↑ Petrocchi-Passeri P, Cero C, Cutarelli A, Frank C, Severini C, Bartolomucci A, Possenti R (June 2015). "The VGF-derived peptide TLQP-62 modulates insulin secretion and glucose homeostasis". Journal of Molecular Endocrinology. 54 (3): 227–39. doi:10.1530/jme-14-0313. PMID 25917832.