As we age, our risk for neurological disorders increases. It is part of life. Why do some people live past 100 years of age and never lose an ounce of brainpower or memory, and others can develop Alzheimer’s disease (AD) in their 50s? We may never know. However, we know a lot and are learning more all the time.
Each disease has a pathway for development. Almost everyone starts with chronic low-level inflammation that grows over time. Oxidative stress results from untreated inflammation, and then a whole world of disease development can occur – depending on the specific disease. When we know that a particular molecule or compound effectively blocks a pathway, that regimen is adopted and refined to address that disease.
Fisetin and Alzheimer’s disease (AD)
https://content.iospress.com/articles/brain-plasticity/bpl200104. This article is lengthy and contains valuable information on fisetin and other neurological disorders – Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), ischemic and hemorrhagic stroke, and traumatic brain injury (TBI). This article will concentrate on fisetin and AD.
First, we must know a bit more about fisetin before going into the pathways of AD and what fisetin can do. Fisetin is an antioxidant that increases glutathione (GSH), a reduced molecule because it is an electron donor that can act as an antioxidant. It also maintains mitochondrial function when oxidative stress levels increase. Fisetin has anti-inflammatory traits that inhibit the 5-lipoxygenase protein enzyme (5LO), which is key to treating AD. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689181/
Fisetin and AD Pathways
Fisetin effectively shuts down and prevents the development of AD pathways in preclinical trials. Anti-inflammatory and oxidative stress are two common pathways for AD to grow in brain tissue. Fisetin consistently prevented cognitive function loss in laboratory animals. Synaptic proteins were maintained at functional levels, and markers of inflammation were reduced. In addition, multiple markers of oxidative stress and lipid peroxidation were noticeably reduced.
Reducing lipid peroxidation is critical in controlling the advancement of AD. Peroxidation of lipids causes changes in membrane permeability and fluidity that impact mitochondria function in the brain. It also alters and inhibits other metabolic processes. https://www.frontiersin.org/research-topics/1269/impact-of-lipid-peroxidation-on-the-physiology-and-pathophysiology-of-cell-membranes
Fisetin also activated the ERK pathway. An extracellular-signal-regulated kinase (ERK) is one pathway the brain uses for signaling and memory. ERK regulates many aspects of cellular function – proliferation, cycle regulation, differentiation, tissue formation, and cell apoptosis (cellular suicide – a normal function over time). https://www.spandidos-publications.com/10.3892/etm.2020.8454
Fisetin also has a proven role in neurotrophic factor production. BDNF (brain-derived neurotrophic factor) is critical for the brain’s nervous system to develop and function properly. BDNF promotes cell survival and differentiation needed in different brain cells. https://www.frontiersin.org/articles/10.3389/fncel.2019.00363/full
5LO (5-lipoxygenase) modulates oxidation and inflammation. The 5LO pathway in AD promotes increases in inflammation in the brain. 5LO and arachidonic acid are interwoven and affect the development of beta-amyloid plaques and tau tangles. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294160/ and https://www.frontiersin.org/articles/10.3389/fncel.2014.00436/full
Fisetin was one of around 30 flavonoids studied as a neuroprotective compound that can prevent a specific type of cell death. Typically, cellular death is termed apoptosis. However, in this case, fisetin stopped ferroptosis (formerly known as oxytosis).
This flavonoid, fisetin, is being clinically evaluated in multiple studies to determine the effectiveness at various dose levels and in conjunction with other compounds – quercetin, isorhamnetin, and luteolin.
Double-blind, randomized, placebo-controlled clinical trials in China are evaluating fisetin and ischemic stroke recovery. There are no clinical trials in the United States currently evaluating fisetin in neurological disorders. The most significant amount of fisetin is found in strawberries. So, would it hurt to add a few more strawberries to your diet? I think not!
Live Longer & Enjoy Life! – Red O’Laughlin – RedOLaughlin.com