ELECTRICA

Cloning of Presenilin 2 cDNA and Construction of Vectors Carrying Effective Mutations in the Pathogenesis of Familial Alzheimer's Disease

1.

Department of Public Health, İstanbul University School of Medicine-Çapa, İstanbul, Turkey

2.

AMBRD Laboratories, İstanbul, Turkey

ELECTRICA 2018; 18: 310-320
DOI: 10.26650/electrica.2018.12050
Read: 649 Downloads: 369 Published: 03 August 2018

Alzheimer's disease (AD) is a neurodegenerative disease and is identified by the detection of amyloid-plaques and neurofibrillary tangles in the brain. Amyloid precursor protein gene, presenilin 1 (PSEN1) gene, and presenilin 2 (PSEN2) gene are responsible for this disease. PSEN2 and amyloid precursor protein (APP) gene mutations are a much rarer cause of familial AD patients. This study aims to clone the PSEN2 gene and create vectors with different mutations by directed mutagenesis. As a result of the experiments, the PSEN2 cDNA was cloned between the BamHI and KpnI cut-off points of the pBluescript II sk (+) vector. PSEN1 and PSEN2 homologs have a role in cell destiny decision and AD progress. We studied some of the PSEN2 mutations (Ala252Thr and Pro334Arg) and provided expression analysis in eukaryotic cell cultures. Amyloid β-protein (Aβ), which is produced by endoproteolytic cleavage of the APP, is considered to play a role in AD. While nominal concentration of Aβ40 is 10 times of Aβ42, the last peptide is firmly linked to AD pathogenesis. Amyloid β-protein is generated by the γ-secretase cleavage of APP onset and the progression of AD, and it is the primary ingredient of the senile plaques. The Aβ42 dodecamer plays a central role in AD. In future studies, it will be determined if there is an increase in Aβ42 protein levels, and the effect on this early onset AD can be identified.

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EISSN 2619-9831