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[P1–212]: CEREBROSPINAL FLUID LEVELS OF ANGIOTENSIN‐CONVERTING ENZYME ARE ASSOCIATED WITH AMYLOID‐β IN ALZHEIMER's DISEASE
Author(s) -
Rocha Natalia P.,
Toledo Andre ASF.,
Corgosinho Laiane TS.,
Cruz de Souza Leonardo,
Paula França Resende Elisa,
Braz Nayara FT.,
Simoes e Silva Ana C.,
Caramelli Paulo,
Teixeira Antonio L.
Publication year - 2017
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.2017.06.032
Subject(s) - cerebrospinal fluid , biomarker , lumbar puncture , medicine , angiotensin converting enzyme , renin–angiotensin system , neurology , central nervous system , alzheimer's disease , endocrinology , disease , blood pressure , psychiatry , chemistry , biochemistry
have investigated the role of trans-acting factors; transcription factor SOX2 and miRNA-140, in ADAM10 gene regulation. The entire sequence of ADAM10 gene is analyzed by computational bioinformatics and screened for probable trans-actors with high regulatory importance. Results: Our study shows that miRNA-140-5p has enhanced expression in AD post-mortem brain hippocampus using high throughput micro-arrays and qRT-PCR. Interestingly we have also seen that miRNA-140 seed sequence is present on both ADAM10 and SOX2 3’UTR and thus reporter constructs containing regulatory elements were transfected into human cell lines along with miRNA-140 mimics and inhibitors to evaluate their interaction by dual luciferase reporter assays. The specific interaction of miRNA-140 with both ADAM10 and its transcription factor SOX2 signifies high regulatory importance of this miRNA in controlling ADAM10 expression.Conclusions:Thus our proposed investigation unravels the mechanisms underlying ADAM10 downregulation bymiR-140 that exacerbates Alzheimer’s disease related neurotoxic effects. Our findings could reflect a strong basis for future research aimed at understanding the potential contribution of trans-acting factors as a biomarker or modulator of AD pathophysiology.