Form and dimensions of aggregates dictate cytotoxicities of Danish dementia peptides.
Familial Danish dementia (FDD) is a neurodegenerative disease which results due to alterations in the BRI2 gene. The pathological symptoms of the disease are cerebral amyloidolysis, parenchymal protein deposits and neuronal degeneration. The ADan peptide is a 34 amino acid long peptide which is thought to be the major cause of amyloid deposition in brains of patients suffering from FDD. Due to the presence of two cysteine residues viz. cys5 and cys23, this peptide exists in two forms: a cyclic oxidized form where the two cysteines form a disulfide bridge and a linear reduced form where the sulphydryl groups of cysteine are free. The relationship between toxicity and structure of the reduced and oxidized forms of ADan peptides has been elucidated by a combination of biophysical and cellular toxicity assays. It is observed that the reduced peptide has a stronger lethal effect on neuronal cell lines compared to its oxidized counterparts at all stages of aggregation. Further, it is observed that the fresh reduced peptide induced greater cell death as compared to its aged counterpart.
Surolia
Ira
I
Department of Biochemistry, South Campus, Delhi University, New Delhi 100021, India.
Sarkar
Debi Prasad
DP
Sinha
Sharmistha
S
D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry; D003704:Dementia / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D018625:Microscopy, Atomic Force; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects*; D010084:Oxidation-Reduction; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011487:Protein Conformation; D017550:Spectroscopy, Fourier Transform Infrared
D048868:Adaptor Proteins, Signal Transducing; D000682:Amyloid; C120083:ITM2B protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D003545:Cysteine