| Autor: |
Windisch, Manfred, Hutter-Paier, Birgit, Rockenstein, Edward, Hashimoto, Makoto, Mallory, Margaret, Masliah, Eliezer |
| Zdroj: |
Journal of Molecular Neuroscience; Aug2002, Vol. 19 Issue 1/2, p63-69, 7p |
| Abstrakt: |
The synaptic protein α-synuclein is a major constitutent of Lewy bodies (LB), pathological neuronal inclusion bodies found in Parkinson’s disease (PD), Alzheimer’s disease (AD), and other neurodegenerative disorders. Owing to data from patient brains, it was speculated that an imbalance between α-synuclein and β-synuclein might be one of the reasons for formation of LBs and the consequent functional deficits. This was supported by the fact that β-synuclein is able to prevent abnormal α-synuclein aggregation. Transgenic mice overexpressing α-synuclein display LB-like inclusions in different brain regions and motor deficits. To verify if re-establishing a normal relation between α-synuclein and β-synuclein is able to prevent the pathology, bigenic mice have been created that overexpress both synucleins. β-synuclein decreased formation of LBs by 40% and prevented functional deficits. This is considered as preliminary in vivo proof of anti-aggregatory function of β-synuclein and its potential as therapeutic substance for treatment of neurodegenerative disorders linked with abnormal protein aggregation. Peptide libraries have been synthesized to explore the active structures of β-synuclein. The first 15 N-terminal amino-acids turned out to be important for the antiaggregatory effect. Further smaller β-synuclein-derived peptides have screened for antiaggregatory and neuroprotective potency in different tissue-culture systems. Preliminary data suggest some of them can be used as leads for further drug development. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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