Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer’s Disease

Abstract

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease, Lewy body dementia, etc. Alzheimer’s Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer’s Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer’s Disease.

Tyramine and Amyloid Beta 42: A Toxic Synergy

“…Diets are often implicated in AD, and various studies have shown protective effects of bioactives to neuronal cells. However, unlike prescription drug studies, it is hard to obtain rigorous data to support dietary interventions [16].…”

Protein Homeostasis Networks and the Use of Yeast to Guide Interventions in Alzheimer’s Disease

“…The cellular environment with a higher level of NAD + activates SIRT1 expression and SIRT1-mediated deacetylation of its targets [285]. In mammals, another important target of SIRT1 is transcription factor EB (TFEB), the master regulator of lysosome biogenesis and autophagy [2]. In addition, DNA damage, metabolic stress, and oxidative damage of cells activates tumor suppressor protein p53 mediated activation of autophagy and cell cycle arrest [286].…”

“…AD is characterized by the accumulation of unwanted toxic protein aggregates including tau neurofibrillary tangles and Aβ aggregates (oligomers, fibrils, and senile plaques) [2]. From previous studies, it has been found that the protein quality control and the cellular defense system has failed severely during AD progression [348].…”

“…Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder, which accounts for 60 to 80% deaths resulting from dementia in elderly people [1]. AD has been found to be a multifactorial disease with several causes being hypothesized and investigated [2]. However, amyloid beta (Aβ) mediated toxicity and its clearance from the neuronal environment has been the most popular area of AD research for the last three decades, as amyloid plaques are the most significant pathological hallmarks of the disease [3].…”

“…The intracellular neuronal environment of AD patients is characterized by loss of proteostasis, mitochondrial dysfunction, impaired mitophagy, oxidative damage, genetic instability, impaired protein clearance, amyloidosis, loss of synapsis, disruption of lipid homeostasis, biometal distribution alteration, and energy failure [2]. Most of these defects are found associated with various events in the AD brain; however, the majority are thought to be the consequence of Aβ overproduction and aggregation [14].…”