DnaJB6 is present in the core of Lewy bodies and is highly up-regulated in parkinsonian astrocytes.
DnaJ/Hsp40 chaperones determine the activity of Hsp70s by stabilizing their interaction with substrate proteins. We have predicted, based on the in silico analysis of a brain-derived whole-genome transcriptome data set, an increased expression of DnaJ/Hsp40 homologue, subfamily B, member 6 (DnaJB6) in Parkinson's disease (PD; Moran et al. [2006] Neurogenetics 7:1-11). We now show that DnaJB6 is a novel component of Lewy bodies (LBs) in both PD substantia nigra and PD cortex and that it is strongly up-regulated in parkinsonian astrocytes. The presence of DnaJB6 in the center of LBs suggests an early and direct involvement of this chaperone in the neuronal disease process associated with PD. The strong concomitant expression of DnaJB6 in astrocytes emphasizes the involvement of glial cells in PD and could indicate a route for therapeutic intervention. Extracellular alpha-synuclein originating from intravesicular alpha-synuclein is prone to aggregation and the potential source of extracellular aggregates (Lee [2008] J. Mol. Neurosci. 34:17-22). The observed strong expression of DnaJB6 by astrocytes could reflect a protective reaction, so reducing the neuronal release of toxic alpha-synuclein and supporting the astrocyte response in PD might limit the progression of the disease process.
Durrenberger
P F
PF
University Department of Neuropathology, Imperial College, University of London, and Hammersmith Hospitals Trust, London, United Kindom.
Filiou
M D
MD
Moran
L B
LB
Michael
G J
GJ
Novoselov
S
S
Cheetham
M E
ME
Clark
P
P
Pearce
R K B
RK
Graeber
M B
MB
D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000473:pathology*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D051844:alpha-Synuclein / Q000378:metabolism
C485565:DNAJB6 protein, human; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D051844:alpha-Synuclein