evaluation of the efficacy of ubisol-q10 treatment in a
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University of Windsor University of Windsor
Scholarship at UWindsor Scholarship at UWindsor
UWill Discover Undergraduate Conference UWill Discover 2016
Mar 29th, 8:30 AM - 9:50 AM
Evaluation of the Efficacy of Ubisol-Q10 Treatment in a Transgenic Evaluation of the Efficacy of Ubisol-Q10 Treatment in a Transgenic
Mouse Model of Alzheimer's Disease Mouse Model of Alzheimer's Disease
Annie S. Kanwar University of Windsor, kanwara@uwindsor.ca
Follow this and additional works at: https://scholar.uwindsor.ca/uwilldiscover
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Kanwar, Annie S., "Evaluation of the Efficacy of Ubisol-Q10 Treatment in a Transgenic Mouse Model of Alzheimer's Disease" (2016). UWill Discover Undergraduate Conference. 2. https://scholar.uwindsor.ca/uwilldiscover/2016/session1/2
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Efficacy of Ubisol-Q10 Treatment in a Transgenic Mouse
Model of Alzheimer’s Disease
ALZHEIMER'S DISEASE
WHAT IS ALZHEIMER’S DISEASE?
Most common neurodegenerative disorder worldwide, affecting 46.8 million individuals
https://cdn.evbuc.com/eventlogos/40265082/old.jpg
• Most common form of
dementia
• Characterized by the
deterioration of neuronal
synapses and widespread
neuronal death in the
brain1
• This produces enlarged
brain ventricles and cortical
shrinkage
WHAT IS ALZHEIMER’S DISEASE?
http://www.synsys.eu/general-public
https://stanfordhealthcare.org/medical-conditions/brain-and-nerves/alzheimers-disease.html
• Two hallmarks of the disease:
1. Amyloid-β Peptide (Aβ) Plaques
2. Neurofibrillary Tangles containing Tau Protein2
• Tau proteins, found abundantly in the CNS, stabilize axonal microtubules
• Tangles are thought to be due to imbalance between Aβ production and clearance2
WHAT IS ALZHEIMER’S DISEASE?
https://www.alzheimer-forschung.de/alzheimer-krankheit/illustrationen_plaquesfibrillen.htm
http://healthland.time.com/2012/02/03/is-alzheimers-caused-by-contagious-proteins/
• Cholinergic neurons specifically
targeted3
• Specific region may be the nucleus
basalis of Meynert – shown to
deteriorate by more than 75%4
• Neuronal cell bodies in the basal
forebrain3
• Innervate many areas of the
cerebral cortex, thus cognitive
functions such as memory are
compromised3
WHICH NEURONS & BRAIN REGIONS ARE
INVOLVED?
https://psychiatricdrugs.com/neurology/acetylcholine/
https://neuroamer.wordpress.com/page/2/
AD SYMPTOMS
Memory loss
Language
problems
Difficulty with simple tasks
Disorientation
Loss of
reasoning
capacity
Loss of
initiative
Behavioural changes
Emotional changes
Lost objects
Difficulty with
elaborate
thoughts
http://www.doc-advice.com/alzheimers-disease/
CURRENT TREATMENTS• No cure
• Symptomatic relief only
• Drug treatments include:5
• Cholinesterase inhibitors –
ReminylER, Exelon, Aricept1
• NMDA receptor antagonists –
Ebixa (Memantine Hydrochloride)
• Non-pharmaceutical treatments:5
• Music therapy
• Pet therapy
• Aromatherapy & massage
• Natural health products
http://www.superama.com.mx/
http://www.lundbeck.com/pt/produtos/neurologia/ebixa
http://www.founduseful.com/natural-health-products-online-and-over-the-phone/
http://www.indexmundi.com/canada/age_structure.html
• Oxidative stress as a possible mechanism for
neurodegeneration6
• What is oxidative stress?
• Some of the O2 we breathe reacts to form
free radicals destabilize essential cell
components
• Damage known as oxidative stress
• Young, healthy strong compensatory/
defense mechanisms to prevent oxidative
damage
• Ageing weakens defenses such that ROS
accumulate apoptosis can be triggered7
PERHAPS OXIDATIVE STRESS?
http://www.kappit.com/tag/hydrogen-jokes/
WHAT IS CoQ10?• CoQ10, part of the ETC, sequesters electrons and stabilizes the mitochondria.
This reduces the oxidative damage taking place. CoQ10 levels decline with age 9
https://www.pinterest.com/pin/488851734528172000/
ARE ANTIOXIDANTS THE ANSWER?
• Antioxidants have been tested
in the past
• Oil-soluble formulation of
Coenzyme-Q10 was assessed
– showed neuroprotection, but
LOW bioavailability8
• Very high effective doses: 400-
1600 mg/kg/day8
• For 70kg human 112g/day8
http://www.drblayney.com/Medical/
WATER-SOLUBLE UBISOL-Q10
CoQ10 α-tocopherol
PEG
NANOMICELLULAR FORMULATION – UBISOL-Q10
COENZYME-Q10
Our NRC collaborators synthesized a water-soluble formulation of CoQ10, known
as Ubisol-Q10 which is much more bioavailable
http://www.longevitylink.com/coenzyme-q10-supplement-facts-for-healthcare-professionals/
• Senescence: in response to stressors and damage, cells can adopt a
permanent state of cell-cycle arrest
PREVIOUS WORK – ALZHEIMER’S DISEASE12
• Autophagy: a cellular stress response in which there is sequestration
and breakdown of harmful or dysfunctional cellular components
• Engulf damaged proteins/ organelles into autophagosome
• Autophagosome fuses with lysosome autolysosome
• Degradation of cellular proteins
• RT2PCR Array analysis showing genes related to autophagy
PREVIOUS WORK – ALZHEIMER’S DISEASE13
SO WHAT NOW?
Can the Ubisol-Q10 formulation provide
neuroprotection in an in vivo animal
model?
http://www.shutterstock.com/similar-44436877/stock-photo-cartoon-of-a-man-who-is-stressed-out-and-develops-hives.html
TRANSGENIC MOUSE MODEL OF AD
• Transgenic mice, predisposed to develop early-onset AD, were
obtained
• Mice had two mutant human genes inserted:
• Human amyloid-precursor protein (APP)
• Human presenilin-1 (PS-1)
PS-1 (γ-secretase complex) APP Aβ
http://www.nature.com/nature/journal/v425/n6958/fig_tab/425565a_F1.html
Obtained transgenic
mice, predisposed
to early-onset AD
Established control &
experimental groups
Monitored mice for
14 months
Obtained blood
samples & sacrificed
mice to extract brains
Performed biochemical analyses &
immunohistochemistry
EXPERIMENTAL DESIGN
Control – regular drinking water
Experimental – Ubisol-Q10 supplemented
water
• ELISA
• RT2PCR
http://ninjuni.cf/how/how-to-draw-a-cartoon-cat-and-mouse.html http://www.how-to-draw-funny-cartoons.com/cartoon-brain.html
http://www.pd4pic.com/test/ http://www.clker.com/clipart-6247.html
IMMUNOHISTOCHEMISTRY – DECREASED
AMYLOID-Β PLAQUES IN BRAIN TISSUE
Control (Untreated) Ubisol-Q10 Treatment WT
Am
yloi
d
50x
Mag
Con
go R
ed
50x
Mag
1 mm
500 um
ELISA – DECREASED AMYLOID-Β LEVEL
IN SERUM
C o n tr o l T r e a te d W ild typ e
0
1 0 0 0
2 0 0 0
3 0 0 0
S e ru m le v e ls o f h u m a n a m y lo id -ß (1 -4 0 )
Hu
ma
n a
my
loid
-ß (
1-4
0)
in p
g/m
l
RT2PCR analyses still underway
FUTURE DIRECTIONS
• Understand if autophagy can be
restored in the in vivo model
through RT2PCR analysis
• Extend to other genetic models of
AD PS-2 , APP10
• Ultimately hope to develop
Ubisol-Q10 as a treatment for
those struggling with
Alzheimer’s disease
REFERENCES1. Alzheimer's disease. (2015, November 8). Retrieved March 25, 2016, from http://www.alzheimer.ca/en/About-
dementia/Alzheimer-s-disease
1. Hardy, J., & Selkoe, D. J. (2002). The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the
Road to Therapeutics. Science, 297(5580), 353-356.
2. Coyle, J. T., Price, D. L., & DeLong, M. R. (1983). Alzheimer's disease: A disorder of cortical cholinergic
innervation. Science, 219(4589), 1184-1190.
3. Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & Delon, M. (1982). Alzheimer's disease and senile
dementia: Loss of neurons in the basal forebrain. Science, 215(4537), 1237-1239.
4. Treatment options. (2015, October 28). Retrieved March 25, 2016, from http://www.alzheimer.ca/en/About-
dementia/Treatment-options
5. Sikorska, M., Lanthier, P., Miller, H., Beyers, M., Sodja, C., Zurakowski, B., . . . Sandhu, J. K. (2014).
Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the
mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: Potential use as an adjuvant treatment in
Parkinson's disease. Neurobiology of Aging, 35(10), 2329-2346.
1. Tieu K (2011) A guide to neurotoxic animal models of Parkin- son’s disease. Cold Spring Harb Perspect Med, 1,
a009316.
2. Sikorska, M., Sandhu, J., & Siyaram, P. (2015, April 16). Solubilized Formulation of CoQ10 for use in Treatment
of Parkinson's Disease. Retrieved from http://www.sumobrain.com/patents/wipo/Solubilized-formulation-coq10-
use-in/WO2015051448A1.pdf
REFERENCES1. Asdf
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9. Ernster, L., & Dallner, G. (1995). Biochemical, physiological and medical aspects of ubiquinone function.
Biochimica Et Biophysica Acta (BBA) - Molecular Basis of Disease, 1271(1), 195-204.
1. Muthukumaran, K., Leahy, S., Harrison, K., Sikorska, M., Sandhu, J. K., Cohen, J., . . . Pandey, S. (2014). Orally
delivered water soluble Coenzyme Q10 (Ubisol-Q10) blocks on-going neurodegeneration in rats exposed to
paraquat: Potential for therapeutic application in Parkinson’s disease. BMC Neuroscience BMC Neurosci, 15(1),
21.
2. Muthukumarana, K., Smith, J., Jasra, H., Sikorska, M., Sandhu, J. K., Cohen, J., . . . Pandey, S. (2014). Genetic
Susceptibility Model of Parkinson’s Disease Resulting from Exposure of DJ-1 Deficient Mice to MPTP: Evaluation
of Neuroprotection by Ubisol-Q10. Journal of Parkinson's Disease, 4, 523-530.
3. Ma, D., Stokes, K., Mahngar, K., Domazet-Damjanov, D., Sikorska, M., & Pandey, S. (2014). Inhibition of stress
induced premature senescence in presenilin-1 mutated cells with water soluble Coenzyme Q10. Mitochondrion,
17, 106-115.
4. Stokes, K. (2015). Ameliorating Presenilin-1 Associated Autophagic & Mitochondrial Dysfunction with Water-
Soluble Co-Enzyme Q10. Thesis, 43-47.
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