Resumption of Autophagy by Ubisol-Q10 in Presenilin-1 Mutated Fibroblasts and Transgenic AD Mice: Implications for Inhibition of Senescence and Neuroprotection
Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Challenges Theme
Open Challenge
Your Location
University of Windsor
Faculty
Faculty of Science
Faculty Sponsor
Dr. Siyaram Pandey
Proposal
Alzheimer’s Disease (AD) is the most common neurodegenerative disorder associated with impaired memory effecting 48 million people worldwide. Currently, the only treatments available are for symptomatic relief, rather than inhibiting its progression. The possible biochemical reasons for AD pathologies are inflammation, mitochondrial dysfunction, increased oxidative stress, and inhibition of autophagy. Previous in vitro experiments have shown that a water-soluble formulation of coenzyme-Q10, Ubisol-Q10, can stabilize the mitochondria, prevent oxidative stress, and inhibit premature senescence in fibroblasts of AD patients. Since autophagy plays a critical role in maintenance and survival of neurons, we hypothesized that Ubisol-Q10 treatment could result in resumption of autophagy. This was observed as we found increased expression of autophagy-related genes beclin-1 and JNK1 following Ubisol-Q10 treatment of AD fibroblasts as well as in the brains of transgenic AD mice. These results were confirmed at the protein level by immunofluorescence and Western blotting. Currently, more Western blots are being conducted to look at expression of other proteins including P21 and LC3. Interestingly, despite reduction of oxidative stress in cells from Ubisol-Q10 treatment, autophagy inhibition leads to resumption of premature senescence in mutated AD fibroblasts indicating that autophagy is critical to prevent the senescence phenotype. Withdrawal of Ubisol-Q10 treatment also leads to the return of the senescence phenotype in AD fibroblasts indicating that constant supplementation is required. Additionally, Ubisol-Q10 supplementation in the drinking water of transgenic AD mice leads to increased expression of beclin-1 and JNK1 in the cortical region. Thus, the activation of autophagy by Ubisol-Q10 could be the mechanism for its ability to halt the progression of AD pathology in transgenic AD mice.
Resumption of Autophagy by Ubisol-Q10 in Presenilin-1 Mutated Fibroblasts and Transgenic AD Mice: Implications for Inhibition of Senescence and Neuroprotection
Alzheimer’s Disease (AD) is the most common neurodegenerative disorder associated with impaired memory effecting 48 million people worldwide. Currently, the only treatments available are for symptomatic relief, rather than inhibiting its progression. The possible biochemical reasons for AD pathologies are inflammation, mitochondrial dysfunction, increased oxidative stress, and inhibition of autophagy. Previous in vitro experiments have shown that a water-soluble formulation of coenzyme-Q10, Ubisol-Q10, can stabilize the mitochondria, prevent oxidative stress, and inhibit premature senescence in fibroblasts of AD patients. Since autophagy plays a critical role in maintenance and survival of neurons, we hypothesized that Ubisol-Q10 treatment could result in resumption of autophagy. This was observed as we found increased expression of autophagy-related genes beclin-1 and JNK1 following Ubisol-Q10 treatment of AD fibroblasts as well as in the brains of transgenic AD mice. These results were confirmed at the protein level by immunofluorescence and Western blotting. Currently, more Western blots are being conducted to look at expression of other proteins including P21 and LC3. Interestingly, despite reduction of oxidative stress in cells from Ubisol-Q10 treatment, autophagy inhibition leads to resumption of premature senescence in mutated AD fibroblasts indicating that autophagy is critical to prevent the senescence phenotype. Withdrawal of Ubisol-Q10 treatment also leads to the return of the senescence phenotype in AD fibroblasts indicating that constant supplementation is required. Additionally, Ubisol-Q10 supplementation in the drinking water of transgenic AD mice leads to increased expression of beclin-1 and JNK1 in the cortical region. Thus, the activation of autophagy by Ubisol-Q10 could be the mechanism for its ability to halt the progression of AD pathology in transgenic AD mice.