Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review

Abstract

Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer’s disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called “nutraceuticals” epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.

Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection

“…Thus, novel approaches in the prevention of neurodegenerative processes could be necessary. One possible solution could be a combination of easily and cheaply available food-derived substances (so-called “nutraceuticals”) with a low profile of adverse reactions, aiming at supporting canonical therapies, targeting the multiple involved pro-inflammatory mediators implicated [ 24 ]. Natural compounds, such as flavonoids, own neuroprotective potential related to their ability to modulate the inflammatory responses involved in neurodegenerative diseases in the microglia [ 25 ].…”

New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases

“…Spermidine plays a protective role in aging heart, and could therefore, be used to protect against CVDs [ 7 , 15 ]. A growing number of studies are reporting that spermidine is a candidate drug for neurodegenerative diseases such as AD and PD, since it can protect neurons, exert anti-inflammatory and antioxidant activities, and induce autophagy [ 113 , 147 ]. In addition, there is increasing evidence that spermidine is a therapeutic agent for metabolic diseases by improving insulin sensitivity, maintaining glucose homeostasis, inhibiting lipid metabolism, and promoting thermogenesis [ 57 , 70 ].…”

Autophagy Modulators in Cancer: Focus on Cancer Treatment

“…Nutraceutical products obtained from normal food can control autophagy. Epigallocatechin gallate (EGCG), a polyphenol compound obtained from green tea, has been reported to modulate autophagy by affecting the balance of the mTOR-AMPK pathway [ 61 , 62 , 63 ]. Fisetin, a member of the flavonoid group of polyphenols, inhibits mTOR activity and induces autophagic-programmed cell death in several cancer cells, including prostate carcinoma and oral squamous cell carcinoma [ 64 , 65 ].…”