Neuronal pentraxin II is highly upregulated in Parkinson’s disease and a novel component of Lewy bodies
Open accessAbstract
Neuronal pentraxin II (NPTX2) is the most highly upregulated gene in the Parkinsonian substantia nigra based on our whole genome expression profiling results. We show here that it is a novel component of Lewy bodies and Lewy neurites in sporadic Parkinson's disease (PD). NPTX2 is also known as the neuronal activity-regulated protein (Narp), which is secreted and involved in long-term neuronal plasticity. Narp further regulates AMPA receptors which have been found to mediate highly selective non-apoptotic cell death of dopaminergic neurons. NPTX2/Narp is found in close association with alpha-synuclein aggregates in both substantia nigra and cerebral cortex in PD but unlike alpha-synuclein gene expression, which is down-regulated in the Parkinsonian nigra, NPTX2 could represent a driver of the disease process. In view of its profound (>800%) upregulation and its established role in synaptic plasticity as well as dopaminergic nerve cell death, NPTX2 is a very interesting novel player which is likely to be involved in the pathway dysregulation which underlies PD.
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The decrease of neuronal pentraxins in Lewy body dementias groups could be due to accumulation of these proteins in Lewy bodies.
“The decrease of neuronal pentraxins in the Lewy body dementias groups corroborates our previous findings [41] and could be due to the accumulation of these proteins in Lewy bodies, as it has been found for NPTX2 in Parkinson’s disease [67].”
NPTX2 was detected in a subpopulation of glial cells, including microglia, in post-mortem tissue of Parkinson's disease patients.
“Additionally, it was detected in a subpopulation of glial cells, including microglia, in post-mortem tissue of Parkinson’s disease (PD) patients (Moran et al. 2008)”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Moran et al. 2008
A whole genome expression profiling revealed NPTX2 to be the most highly upregulated gene in the substantia nigra of sporadic PD patients.
“A whole genome expression profiling revealed NPTX2 to be the most highly upregulated gene in the substantia nigra of sporadic PD patients (Moran et al. 2008).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Moran et al. 2008
Synaptic dysfunction contributes to disease pathogenesis in PD and may be linked to cognitive and motor dysfunction.
“Synaptic dysfunction contributes to disease pathogenesis in PD (Nguyen et al. 2019) and may be linked to cognitive and motor dysfunction (Bereczki et al. 2017; Moran et al. 2008).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Moran et al. 2008
NPTX2 accumulated in Lewy bodies and neurites in substantia nigra and cerebral cortex.
“Additionally, it accumulated in Lewy bodies and neurites in substantia nigra and cerebral cortex (Moran et al. 2008).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Moran et al. 2008
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- Authors
- Moran, L. B., Hickey, L., Michael, G. J., Derkacs, M., Christian, L. M., Kalaitzakis, M. E., Pearce, R. K. B., & Graeber, M. B.
- Affiliations
- Hammersmith Hospital (GB)
- University of London (GB)
- Corresponding author
- Graeber, Manuel B.
- ORCID
- Michael, Gregory J.
- Venue
- Acta Neuropathologica
- Published
- 2007-11-07
- Volume
- 115
- Issue
- 4
- Pages
- 471-478
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC2270353
- OpenAlex
- W1970866871
- Cited by
- 69
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 4 · 2018: 6 · 2016: 3 · 2015: 5 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Neuropathologica (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Parkinson's UK (G-4028, 948776)
- Multiple Sclerosis Society
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- NPTX2, Parkinson's disease, Lewy bodies, Lewy neurites, alpha-synuclein aggregates, substantia nigra, dopaminergic neuron death, AMPA receptors, gene expression profiling, synaptic plasticity
- MeSH terms
- Pentraxins, C-Reactive Protein, Frontal Lobe, Humans, Nerve Tissue Proteins, Parkinson Disease, Substantia Nigra, Up-Regulation, Lewy Bodies, alpha-Synuclein
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