Title

Amelioration of Autophagic and Mitochondrial Defects in PS-1 Mutated cells

Type of Proposal

Oral presentation

Start Date

24-3-2015 2:00 PM

End Date

24-3-2015 2:50 PM

Faculty

Faculty of Science

Faculty Sponsor

Dr.Pandey

Importance of the Project

A water-soluble formulation of CoQ10 (WS-CoQ10) was shown to stabilize mitochondria and prevent oxidative 20 Q4 stress-induced neuronal death. Presenilin-1 (PS-1)-mutated Alzheimer's Disease (AD) fibroblasts (PSAF) were 21 used for studying the effects of PS-1 mutation. PS-1 mutation correlated to increased reactive oxygen species 22 (ROS) production and stress induced premature senescence (SIPS) in PSAF; WS-CoQ10 treatment decreased 23 ROS generation, increased population doublings, and postponed SIPS. Treated PSAF had higher PCNA expression, 24 and lower levels ofMnSOD, p21, p16Ink4A, and Rb.WS-CoQ10 caused the resumption of autophagy in PSAF. Thus, 25 WS-CoQ10 as inhibitor of SIPS and ameliorator of autophagy could be an effective prophylactic/therapeutic agent 26 for AD.

Existing State of Knowledge

Co-Q10 is an electron transport chain intermediate that has been seen to provide antioxidative effects. Unfortunately it it has been shown to have low bio-availability in vivo as it is a lipid soluble molecule. The formulation we are working with uses nano-micelles as a vector which increases int availability and activity in the bran.

Research Question

Does prophylactic treatment with water soluble Co-Q10 work to ameliorate Alzheimer's disease in PS-1 mutated fibroblasts, and the mechanisms which underlie the disease?

Methodology

Culturing PS-1 mutate fibroblasts in the presence and absence of Q10. PS1 is a common familial mutation in Alzheimer's disease.Assays will be done to see the longevity of the cells treated with or without Q10.Additional assays will be done to evaluate the effect Q10 has on specific proteins and pathways associated with the progression of Alzheimer's diseases.

Your Findings

We have shown that Q10 delays stress induced premature senescence of Alzheimer diseased fibroblasts though several possible mechanisms including pro-survival autophagy, anti oxidation, and decrease in proteins associated with the disease such as amyloid beta and phosphorylated tau.

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Mar 24th, 2:00 PM Mar 24th, 2:50 PM

Amelioration of Autophagic and Mitochondrial Defects in PS-1 Mutated cells