Neuronal pentraxin II is highly upregulated in Parkinson's disease and a novel component of Lewy bodies.
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.
Moran
Linda B
LB
Imperial College London and Hammersmith Hospitals Trust, University Department of Neuropathology, Charing Cross campus, Fulham Palace Road, London W6 8RF, UK.
Hickey
Lorraine
L
Michael
Gregory J
GJ
Derkacs
Maria
M
Christian
Lynne M
LM
Kalaitzakis
Michail E
ME
Pearce
Ronald K B
RK
Graeber
Manuel B
MB
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
D002097:C-Reactive Protein; D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D000099153:Pentraxins; C497604:SNCA protein, human