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NPTX2

Official Full Name
neuronal pentraxin 2
Organism
Homo sapiens
GeneID
4885
Background
This gene encodes a member of the family of neuronal petraxins, synaptic proteins that are related to C-reactive protein. This protein is involved in excitatory synapse formation. It also plays a role in clustering of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors at established synapses, resulting in non-apoptotic cell death of dopaminergic nerve cells. Up-regulation of this gene in Parkinson disease (PD) tissues suggests that the protein may be involved in the pathology of PD. [provided by RefSeq, Feb 2009]
Synonyms
NP2; NARP; NP-II;

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Detailed Information

Neuronal pentraxin Ⅱ(NPTX2) belongs to the neuron pentamer protein family, but its distribution is widespread and not limited to the nervous system. Recently, it has been found that NPTX2 is associated with the occurrence of malignant glioma, Parkinson's disease, narcolepsy, drug addiction, lung cancer, pancreatic cancer and other diseases.

The Features of NPTX2

At present, most researches of the NPTX2 gene are focused on the nervous system. First, NPTX2 has a calcium-dependent lectin, which combines with NPTX1 and NPTXR to form an extracellular synaptic scaffold protein complex, which can promote the occurrence and remodeling of pyramidal neurons in the hippocampus and cerebral cortex. And it specifically mediates fast excitatory synaptic transmission by specifically binding to the AMPA receptor subunit. And the overexpression of NPTX2 can effectively increase the formation of excitatory synapses. Second, NPTX2 is similar to the acute phase reaction protein of inflammation, which can bind and remove extracellular pathogens, synaptic fragments and neuron toxins by activating the complement system, and has potential neuroprotective effects. Finally, NPTX2 can regulate axon structure by labeling specific synaptic sites to degrade or renew proteins, and it also plays a role in synapse formation in the visual nervous system at the developmental stage.

Nptx2Figure 1. The targeting of NPTX2 and NPTXR inhibits neuroblastoma. (Bartolini, A., et al. 2015)

NPTX2 and Neurological Diseases

The study found that some patients with malignant glioma had no significant changes in edema and tumor burden after receiving vascular endothelial growth factor (VEGF) inhibitor treatment. Among them, there are some gliomas in which the expression of VEGF is lost. Among these cell tumors, the expression of NPTX2 in patients with edema type is significantly higher than that in patients with non-edema type (about 7 times), which is a predictive index of edema tumors. NPTX2 is closely related to the expression of water channel 3, which may be related to certain VEGF-dependent edema malignant gliomas.

According to the study of the gene expression profile of Gene Chip, NPTX2 is the gene with the highest degree of up-regulation in Parkinson's disease, and it is also a new component of sporadic Parkinson's Lewy bodies and Lewy neurites. NPTX2 has the function to participate in the removal of presynaptic substances. In Parkinson's disease, the dysfunction of synapse is obvious, and the appearance of NPTX2 in Lewy bodies may be related to this. Since the discovered AMPA receptor is a regulator of non-apoptotic cell death in dopaminergic neurons, and NPTX2 is closely related to the AMPA receptor, NPTX2 may be an important role in the pathway disorder of Parkinson's disease.

NPTX2 and Tumor

Neuroblastoma (NB) is a kind of extracranial malignant solid tumor that is more common in children under 5 years old. Its occurrence is extensive and fast-growing, and multiple metastases occur early. Bartolini et al. found that NPTX2 and NPTXR are overexpressed in NB, and using targeting agents to block the NPTX2 pathway can affect the interaction between tumor cells and their microenvironment, and ultimately inhibit the production and development of NB. This study suggests that NPTX2 gene may be a potential poor prognostic biomarker and therapeutic target for NB patients.

In human pancreatic cancer cell lines and 25 patients with primary pancreatic cancer, the promoter region of the NPTX2 gene was found to be largely unmethylated in normal pancreatic tissue. However, it is frequently hypermethylated in pancreatic cancer cells, and shows full or partial methylation of NPTX2 in all cancer tissues. In addition, NPTX2 was detected at the mRNA level in normal and tumor tissues of the same patient, but the average level in cancer tissue was significantly lower than that of adjacent normal tissues.

References:

  1. Bartolini, A. , Di Paolo, D. , Noghero, A. , Murgia, D. , Sementa, A. R. , & Cilli, M. , et al. (2015). The neuronal pentraxin-2 pathway is an unrecognized target in human neuroblastoma which also offers prognostic value in patients. Cancer Research, 0008-5472.CAN-15-0649.
  2. Swanson, A. , & Willette, A. A. . (2016). Neuronal pentraxin 2 predicts medial temporal atrophy and memory decline across the alzheimer’s disease spectrum. Brain, Behavior, and Immunity, S0889159116303427.
  3. Karagkounis, G. , Thai, L. , Devecchio, J. , Gantt, G. A. , Duraes, L. , & Pai, R. K. , et al. (2016). Nptx2 is associated with neoadjuvant therapy response in rectal cancer. Journal of Surgical Research, 202(1), 112-117.
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