PMID- 10407019
OWN - NLM
STAT- MEDLINE
DCOM- 19990802
LR  - 20191023
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 14
DP  - 1999 Jul 15
TI  - alpha-Synuclein shares physical and functional homology with 14-3-3 proteins.
PG  - 5782-91
AB  - alpha-Synuclein has been implicated in the pathophysiology of many
      neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's
      disease. Mutations in alpha-synuclein cause some cases of familial PD
      (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many
      neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic
      neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that
      alpha-synuclein shares physical and functional homology with 14-3-3 proteins,
      which are a family of ubiquitous cytoplasmic chaperones. Regions of
      alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition,
      alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to
      associate with 14-3-3, including protein kinase C, BAD, and extracellular
      regulated kinase, but not Raf-1. We also show that overexpression of
      alpha-synuclein inhibits protein kinase C activity. The association of
      alpha-synuclein with BAD and inhibition of protein kinase C suggests that
      increased expression of alpha-synuclein could be harmful. Consistent with this
      hypothesis, we observed that overexpression of wild-type alpha-synuclein is
      toxic, and overexpression of alpha-synuclein containing the A53T or A30P
      mutations exhibits even greater toxicity. The activity and binding profile of
      alpha-synuclein suggests that it might act as a protein chaperone and that
      accumulation of alpha-synuclein could contribute to cell death in
      neurodegenerative diseases.
FAU - Ostrerova, N
AU  - Ostrerova N
AD  - Department of Pharmacology, Loyola University Medical Center, Maywood, Illinois
      60153, USA.
FAU - Petrucelli, L
AU  - Petrucelli L
FAU - Farrer, M
AU  - Farrer M
FAU - Mehta, N
AU  - Mehta N
FAU - Choi, P
AU  - Choi P
FAU - Hardy, J
AU  - Hardy J
FAU - Wolozin, B
AU  - Wolozin B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for
      Neuroscience
JID - 8102140
RN  - 0 (14-3-3 Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SNCA protein, human)
RN  - 0 (Synucleins)
RN  - 0 (alpha-Synuclein)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - 14-3-3 Proteins
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Enzyme Inhibitors/chemistry/metabolism
MH  - Gene Expression Regulation
MH  - Humans
MH  - Molecular Sequence Data
MH  - Nerve Tissue Proteins/*chemistry/genetics/*metabolism
MH  - Phosphoproteins/chemistry/metabolism
MH  - Point Mutation
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Proteins/*chemistry/genetics/*metabolism
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Synucleins
MH  - Transfection
MH  - *Tyrosine 3-Monooxygenase
MH  - alpha-Synuclein
PMC - PMC6783081
EDAT- 1999/07/17 00:00
MHDA- 1999/07/17 00:01
CRDT- 1999/07/17 00:00
PHST- 1999/07/17 00:00 [pubmed]
PHST- 1999/07/17 00:01 [medline]
PHST- 1999/07/17 00:00 [entrez]
PST - ppublish
SO  - J Neurosci. 1999 Jul 15;19(14):5782-91.