Article

Neural expression profile of α-synuclein in developing human cortex

Department of Psychiatry, University of Bonn Medical Center, Germany.
Neuroreport (Impact Factor: 1.64). 10/1999; 10(13):2799-803.
Source: PubMed

ABSTRACT Alpha-synuclein is a predominantly neuronal presynaptic protein that may play an important role during synaptogenesis and CNS development. In order to elucidate the human developmental expression profile, we used a polyclonal antiserum against the NAC domain of alpha-synuclein. In normal fetal cortex neuroectodermal precursor cells elicited staining in the soma, whereas, in adult cortex, we observed a staining pattern compatible with synaptic function. The same developmental intraneuronal redistribution was found in neurodegenerative disorders, i.e. somatic staining in neuroectodermal precursors in fetal (trisomy 21) and a synaptic pattern in adult (Down's syndrome, Alzheimer's disease) brains. RT-PCR and Western blot analysis revealed expression at all time points studied (4-7.5 months) during human brain development.

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    • "Very recent data demonstrate that extreme aneuploidy is selected against in neurodevelopment.74 Multiple lines of evidence point to an important developmental role for SNCA, first in neuronal differentiation and later in synaptogenesis,75,76 with prominent perikaryal expression of SNCA in early development in the same neuronal groups later affected in PD.77 Therefore, we can speculate that certain somatic SNCA variants could be beneficial to neurons or their precursors in early development, undergoing positive selection within the organism, with PD a much later adverse consequence. "
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    • "The studies described above do not yet amount to a consistent understanding of α-synuclein expression in idiopathic PD, and indicate that altered α-synuclein protein levels can occur independently of altered mRNA levels. This phenomenon has been reported in a comparison between fetal and adult α-synuclein expression, where protein levels are higher in the adult without a corresponding increase in mRNA (Bayer et al., 1999). Aging is associated with decreased brain α-synuclein mRNA (Li et al., 2004b and the present study). "
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    • "The studies described above do not yet amount to a consistent understanding of α-synuclein expression in idiopathic PD, and indicate that altered α-synuclein protein levels can occur independently of altered mRNA levels. This phenomenon has been reported in a comparison between fetal and adult α-synuclein expression, where protein levels are higher in the adult without a corresponding increase in mRNA (Bayer et al., 1999). Aging is associated with decreased brain α-synuclein mRNA (Li et al., 2004b and the present study). "
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