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P2‐239: Rapid transmission of exogenous beta‐amyloid peptides from blood to the brain
Author(s) -
Zhang Wandong,
Xiong Huaqi,
Shen Shanshan,
Callaghan Debbie,
Huang Peilin,
Njoo Howard,
Wu Jun
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.1288
Subject(s) - immunohistochemistry , peptide , genetically modified mouse , amyloid beta , chemistry , amyloid (mycology) , amyloidosis , pathology , transgene , biochemistry , medicine , gene
of inhibition is indicated by the lack of similar inhibition of OGG1. Furthermore, Fe(II) inhibits NEIL1’s interaction 4to 6-fold with the downstream repair enzymes DNA polymerase b (Polb) and flap endonuclease-1 (FEN1), a prerequisite for efficient repair of 5-hydroxy uracil (5-OHU), a common base lesion product of cytidine. As expected, Fe(II/III) and Cu(II) inhibited NEIL-initiated complete repair. Further, we also found inhibition of mitochondrial BER in SH-SY5Y cells treated with MPTP and/or Fe and correlated with accumulation of mitochondrial DNA damage in Parkinson’s cell culture model. Specific metal chelators and the natural chemopreventive compound curcumin reversed NEILs’ inhibition both in vitro and in cells. Conclusions: Excess accumulation of transition metals in PD brain can act as a ‘double edged sword’ by inducing DNA damage (by ROS formation) and also by blocking DNA repair. The study provides evidence to inhibiton of repair of oxidative DNA damage by etiological factors of PD and correlation to accumulation of oxidized DNA bases in human brain dopaminergic neurons, and importantly develop potential strategies to reverse this inhibition using natural compounds (e.g. curcumin) for improved therapeutic intervention of PD.