Date of Award

4-2015

Document Type

Thesis

Primary Advisor

Dr. Todd Schraw

Abstract

As a devastating neurological condition that expends millions of lives each year, Alzheimer’s disease (AD) is a subject of intense investigation.1 Although AD has been known for over a century, the precise mechanisms that underlie AD pathogenesis and development are still poorly understood. The Alzheimer phenotype is typified by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), causing researchers to notice several key enzymes implicated in this process.1 Most notable are β and γ secretases (which drive Aβ plaque production) and phospholipase

A2 (which stimulates major cascade activation through the specific cleavage of fatty acyl esters).2 Both acidic and neutral sphingomyelinases of the ceramide pathway are also strongly linked to AD development and progression.3,4 As a specific type of esterase, PLA2 specializes in phospholipid catabolism by specifically cleaving fatty acyl bonds at the sn-2 position, producing a free fatty acid and lysophospholipids as products.3,5 This stimulates the arachidonic acid (AA) cascade, while lipid cleavage by sphingomyelinase upregulates the ceramide pathway.3 Cyclooxygenase (COX) and lipooxygenase (LOX) are suspected to be key players in oxidative and neurological damage and are involved in both these metabolic pathways.4,5 A further investigation of these molecular messengers and their cellular environments is absolutely essential for therapeutic intervention and effective medical treatments. Recently, the role of herbal medicines has been investigated to produce possible leads for Alzheimer’s treatment. Turmeric contains over 20 medicinally useful compounds, of which curcumin is a key component.6 In this review, we hypothesize that turmeric will prove especially useful in preventing amyloid-β plaque deposition in early stages of AD and improvement of learning and coordination in middle stages of the disease. Further evidence suggests curcumin’s efficacy in resisting ROS, preventing tau aggregation, and limiting the spread of pro-inflammatory molecules throughout the body. Because of its highly beneficial effects as an Alzheimer therapeutic, we commend that turmeric be studied in greater detail and incorporated into Western medical treatments. Additionally, a prospective study will be presented to determine the efficacy of turmeric therapies, both in improving physical activities and overall neurological health. Although turmeric’s precise mechanisms are not yet understood, multiple studies have confirmed its beneficial effects in preventing amyloidogenesis by modulating esterase and sphingomyelinase activities and also resisting misdirected cleavage of APP.2 Turmeric has also been found to downregulate abnormal GSK-3β function and prevent formation of SPs and NFTs. Interestingly, murine models subjected to a turmeric regimen not only displayed a reversal of AD symptoms, but also demonstrated a lower susceptibility to neurodegenerative disease.3 Collectively, these findings strongly support turmeric’s therapeutic use in Western medicine.

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