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Mapping of amyloidogenic peptides induced genotoxicity in relevance to neuronal cell death

Ramesh, B. N. (2010) Mapping of amyloidogenic peptides induced genotoxicity in relevance to neuronal cell death. PhD thesis, University of Mysore.

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Abstract

Amyloidogenic peptides play an important role in neurodegeneration. Recently, there are reports on the nuclear localization of amyloids and proposed to have implications to DNA damage and neuronal apoptosis. The mechanism of amyloidogenic peptides induced neuronal cell death is still not clear. Our main questions are, (i) mapping of amyloidogenic peptides induced genotoxicity; (ii) A(1-42) induced genomic instability in aged rabbits and (iii) to study anti-amyloidogenic properties of indigenous plants. To achieve these objectives we have employed agarose gel, Tm, EtBr binding, DNase I sensitivity assay, CD, MRI and TEM techniques. The results are summarized as follows: (i) A fragments (1-11, 1-28, 1-40 and 1-42) nick scDNA and causes the open circular and linear forms. The Mg2+ ion enhanced the nicking activity of A fragments (1-11, 1-28, 1-40 and 1-42). The modification of histidine of A(1-11) abolished the DNA nicking activity. The DNA instability by studying Tm and EtBr binding revealed that DNA became unstable in presence of different fragments of A. (ii) The aged (4 yr) New Zealand rabbits were intracisternally injected with A(1-42) and DNA analyzed from aged rabbits for stability showed that DNA is damaged in FC and H; where as in M, DNA is in condensed state. The DNA conformation study evidenced the presence of C,  and - type DNA conformations in FC, H and M of A(1-42) injected (25 days) rabbit brain regions respectively. MRI studies showed no significant changes in brain structures between control and A(1- 42) injected aged rabbit brain regions. MRI scanning before and after 45 days of A injection found significant reduction in the thickness of hippocampus, temporal lope, frontal lobe, and midbrain and an increase in lateral ventricle volume. Additionally, the aqueous leaf extracts of C. crista and C .asiatica could not prevent the DNA nicking activity of A(1-42). The CG and VG induced modified conformations in A(1-11), A(1-28) and A(25-35). The aqueous extracts of C. crista and C. asiatica showed anti-oxidant and anti-inflammatory activities. The C. crista showed antiamyloidogenic properties.

Item Type: Thesis (PhD)
Uncontrolled Keywords: Amyloidogenic peptides, neurodegeneration, C. crista, C .asiatica
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 25 Peptide Chemistry
600 Technology > 01 Medical sciences > 17 Toxicology
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 15 May 2012 06:30
Last Modified: 15 May 2012 06:30
URI: http://ir.cftri.com/id/eprint/10753

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