PMID- 10557341
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 23
DP  - 1999 Nov 9
TI  - Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains
      alpha-, beta-, and gamma-synuclein.
PG  - 13450-5
AB  - Pathogenic alpha-synuclein (alphaS) gene mutations occur in rare familial
      Parkinson's disease (PD) kindreds, and wild-type alphaS is a major component of
      Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of 
      Alzheimer's disease, but beta-synuclein (betaS) and gamma-synuclein (gammaS) have
      not yet been implicated in neurological disorders. Here we show that in PD and
      DLB, but not normal brains, antibodies to alphaS and betaS reveal novel
      presynaptic axon terminal pathology in the hippocampal dentate, hilar, and CA2/3 
      regions, whereas antibodies to gammaS detect previously unrecognized axonal
      spheroid-like lesions in the hippocampal dentate molecular layer. The aggregation
      of other synaptic proteins and synaptic vesicle-like structures in the alphaS-
      and betaS-labeled hilar dystrophic neurites suggests that synaptic dysfunction
      may result from these lesions. Our findings broaden the concept of
      neurodegenerative "synucleinopathies" by implicating betaS and gammaS, in
      addition to alphaS, in the onset/progression of PD and DLB.
FAU - Galvin, J E
AU  - Galvin JE
AD  - Department of Neurology, Medical College of Pennsylvania, Hahnemann University,
      245 North 15th Street, Philadelphia, PA 19129, USA.
FAU - Uryu, K
AU  - Uryu K
FAU - Lee, V M
AU  - Lee VM
FAU - Trojanowski, J Q
AU  - Trojanowski JQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (SNCA protein, human)
RN  - 0 (SNCB protein, human)
RN  - 0 (Synucleins)
RN  - 0 (alpha-Synuclein)
RN  - 0 (beta-Synuclein)
RN  - 0 (gamma-Synuclein)
SB  - IM
MH  - Axons/*pathology
MH  - Hippocampus/metabolism/*pathology/ultrastructure
MH  - Humans
MH  - Lewy Body Disease/metabolism/*pathology
MH  - Microscopy, Electron
MH  - Nerve Tissue Proteins/*metabolism
MH  - Parkinson Disease/metabolism/*pathology
MH  - Synucleins
MH  - alpha-Synuclein
MH  - beta-Synuclein
MH  - gamma-Synuclein
PMC - PMC23968
EDAT- 1999/11/11 00:00
MHDA- 1999/11/11 00:01
CRDT- 1999/11/11 00:00
PHST- 1999/11/11 00:00 [pubmed]
PHST- 1999/11/11 00:01 [medline]
PHST- 1999/11/11 00:00 [entrez]
AID - 10.1073/pnas.96.23.13450 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13450-5. doi:
      10.1073/pnas.96.23.13450.