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Page 36

September 16-17, 2019 | Paris, France

Dementia and Alzheimer's Disease

World Congress on

Journal of Clinical Psychiatry and Cognitive Psychology | Volume: 03

Studies on the role of DNAdynamics inNeurodegeneration: Newchallenges and excitements

Jagannatha Rao KS

INDICASAT AIP, Republic of Panama

NA is adynamic and crucialmoleculewhose conformation

kinetics plays a major role in biological function. Reports

from our lab and elsewhere indicated the presence of non-

BDNA forms of conformations in neurodegenerative diseases

like Fragile X-syndrome, Huntington's chorea, Alzheimer's

and others. Recently, our laboratory discovered the presence

of Z-DNA in the hippocampal region of severely affected

Alzheimer's disease (AD) brain samples and modified

B-conformation in Parkinson disease. The alternate purine–

pyrimidine bases are the potential sequences adopting

Z-DNA, and these are present in the promoter regions of AD

specific genes like amyloid precursor protein (APP), Presenilin

and ApoE. We hypothesized that Z-DNA might be involved

in the expression of these pathologically important genes.

In the present paper, we have developed theoretical model

on the possible mechanisms/hypothetical proposition of

Z-DNA transition and its implications in AD. We developed a

model where we try to understand that Z-DNA is formed in

the promoter region of the APP, and Presenilin genes and

this conformation may absorb the negative supercoils at that

region. The decrease in the supercoil density alters the native

supercoiling domain and positively regulates gene expression

of like APP and Presenilin. We further try to understand that

Z-DNA may be involved in the down regulation of genes

involved in Aβ clearance defense mechanisms in AD. The

proposed model tries to understand the AD behavioral

pathology like emotions, eating behavior memory loss, and

coordination failure.