title: Neuronal pentraxin II is highly upregulated in Parkinson's disease and a novel component of Lewy bodies.
abstract: 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.
authors.affiliation: Imperial College London and Hammersmith Hospitals Trust, University Department of Neuropathology, Charing Cross campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Moran
authors.forename: Lorraine
authors.initials: L
authors.lastname: Hickey
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Michael
authors.forename: Maria
authors.initials: M
authors.lastname: Derkacs
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Christian
authors.forename: Michail E
authors.initials: ME
authors.lastname: Kalaitzakis
authors.forename: Ronald K B
authors.initials: RK
authors.lastname: Pearce
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Graeber
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology*; D013378:Substantia Nigra / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D051844:alpha-Synuclein / Q000378:metabolism; D000099153:Pentraxins
chemical_list: D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D000099153:Pentraxins; C497604:SNCA protein, human