Why is it such a challenge to treat or prevent Alzheimer’s vs. cancer?

Although cancer and Alzheimer’s disease are among the most feared diseases in adults, we are developing solutions for cancer but not Alzheimer’s. Consequently, new multi-target approaches need to be explored for Alzheimer’s.

Cancer is caused by the uncontrolled growth, spread, and invasion of malignant cells in the body. To prevent or treat cancer, we simply need to find one or combination of different ways to remove cancer, kill cancer cells, or stop cancer cells from growing and proliferating. The advancements of cancer research have resulted in early detection and developments of many cancer drugs or therapies. Cancer treatments range from surgery to remove cancer, radiotherapy and chemotherapy that kill cancer cells but also inflict injury or death to normal cells, to safer and more precise immuno- and gene therapies that cause cancer cell death without much harm to normal cells. Combination of surgery with the other different therapies is often used. With these advancements, many cancer patients now survive and heal. Likely cancer will be cured in near future.

The situation for Alzheimer’s is different - Alzheimer’s is a progressive disease characterized by death of large number of brain cells or neurons and destruction of neural connections and significant loss of brain mass. The symptoms include a decline in memory, cognition, and other abilities. It is known an adult human brain largely keeps using the same neurons one is born with, thus neuron regeneration or neurogenesis does not happen in most parts of human brain. Once neurons die in those parts of brain, there is no replacement. Only in recent years has brain research confirmed that neurogenesis happens in two brain areas, the hippocampus and subventricular zone1. The hippocampus is the area important for memory formation and cognitive functions, scientists also find hippocampal neurogenesis is abundant in healthy adults but drops sharply in patients with Alzheimer’s2,3. Therefore, to prevent and treat Alzheimer’s, an effective product or therapy must be able to protect neurons from death and enhance neurogenesis. However, there are many internal and external factors can cause neuron death and interfere neurogenesis. The current approach of drug development by targeting single cause or biomarker is not going to find a “magic bullet” for Alzheimer’s. In fact, a series of major pharmaceutical companies’ Phase III studies focusing on clearing out or preventing amyloid-β (Aβ) accumulation in the brain or targeting other single biomarkers have all failed.

Alzheimer’s is caused by a combination of factors that affect the brain over time. Many health, environmental, and lifestyle risk factors have been implicated in causing harm and death of neurons and Alzheimer’s. As we age, our blood-brain barrier, a defense layer to keep out toxins and pathogens from the brain, gets compromised and the brain is more liable to harms of the risk factors. Studies have linked alcohol, stroke, sleep disorders, bacteria in the mouth, and traumatic brain injury to higher risk of Alzheimer’s. Other risk factors include CVD, diabetes, hypertension, chronic stress, depression, smoking, virus, drugs, toxins, unhealthy diet, social and physical isolation, etc. All these risk factors potentially induce inflammation, immune response, heighten levels of oxidative radicals, amyloid-β (Aβ), tau protein and a series of toxic events in the brain that lead to loss of neural connection, damage and death of neurons. So, what is the best way to address the multiple risk factors?

Natural product research in recent years has led to new discoveries of plants and its constituents having potential in prevention and treatment of Alzheimer’s. Some of these natural constituents with excellent multi-target, neuroprotective, memory and cognitive enhancing effects are found from spices and food sources. The world’s most expensive spice saffron (Crocus sativus) and its main constituent crocin have been found in recent years to have amazing effects on improving memory and cognition in patients with mild cognitive impairments and Alzheimer’s4. At least 4 clinical studies showed saffron results in neurocognitive improvements. Results from a one-year study also indicated saffron improves brain activities and likely neurogenesis. A small volume increase was observed in area of hippocampus of patients who used saffron. Additionally, at least 4 other human studies of Saffron in combination with other herbs also resulted improvements memory and cognition in patients with cognitive impairments, vascular dementia and major neurocognitive disorders. Crocin, the main active constituent responsible for health effects of saffron, has been extensively investigated in animal and human studies lately. Crocin not only has potent antioxidant and anti-inflammatory effects, but also exhibits multi-target neuroprotective effects against various risk factors, tightening blood-brain barrier, improving memory and cognition, and enhancing neurogenesis. Other natural constituents with potential effects for Alzheimer’s include curcumin from turmeric5, EGCG from green tea6,7, nobiletin and tangeretin from citrus8. Studies also reveal active constituents from some traditional herbs, such as Panax ginseng, Rhodiola rosea, and Ginkgo biloba, having neuroprotective and cognitive deficit improving effects. These mentioned spices or food plants or traditional herbs have long histories of human use and good safety profiles. Herbal medicines have the potential to be developed into effective natural alternative for Alzheimer’s because of its multi-function, multi-target characteristics9,10. Due to contents of active constituents in herbal plants vary significantly and are not all well characterized, herbal medicines have issues including inconsistency in quality and efficacy. With the natural active constituents identified and confirmed by human and animal studies, the active constituents can be extracted, purified and then formulated in multi-component products. A product made with these pure constituents, either in forms of pharmaceuticals or nutraceuticals, can consistently deliver synergistic and multi-target effects for neuroprotection, neurogenesis, memory and cognition improvements. This natural multi-target approach could be proven as the best solution for the prevention and treatment of Alzheimer’s over time.

For more information about natural solution for Alzheimer’s and other age-related diseases, please check out other blogs and products in the website https://saffronhealthsci.com/.

 

References:

  1. Tobin MK, et al. (2019), Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer’s Disease Patients. Cell Stem Cell, 2019, 24: 974–982.
  2. Moreno-Jiménez EP, et al. (2019) Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nature Medicine, 2019, 25: 554-560.
  3. Scopa C, et al. (2020) Impaired adult neurogenesis is an early event in Alzheimer’s disease neurodegeneration, mediated by intracellular Aβ oligomers. Cell Death Differ 2020, 27: 934-948
  4. Finley JW & Gao S. (2017) Perspective on Crocus sativus L. (Saffron) Constituent Crocin: A Potent Water-Soluble Antioxidant and Potential Therapy for Alzheimer’s Disease. Agric. Food Chem. 2017, 65, 1005−1020.
  5. Small GW, et al. (2018) Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial. Am J Geriatr Psychiatry, 2018, 26: 266-277.
  6. Tomata Y, et al. (2016) Green Tea Consumption and the Risk of Incident Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. Am J Geriatr Psychiatry 2016, 24: 881-889.
  7. Pervin M, et al (2017) Blood brain barrier permeability of (−)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice. Biochemistry and Biophysics Reports, 2017, 9: 180-186.
  8. Braidy N, et al. (2017) Neuroprotective Effects of Citrus Fruit-Derived Flavonoids, Nobiletin and Tangeretin in Alzheimer’s and Parkinson’s Disease. CNS Neurol Disord Drug Targets. 2017, 16(4): 387-397.
  9. Kim HG, et al (2012) Herbal Medicines for the Prevention and Treatment of Alzheimer's Disease.  Current Pharmaceutical Design, 2012, 18: 57-75.
  10. Singh A, et al. (2020) Age related neurodegenerative Alzheimer’s disease: Usage of traditional herbs in therapeutics. Neurosci Lett. 2020, 717: 134679.

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