The targeting of Alzheimer’s disease (AD) with mixtures of non-toxic pleiotropic natural compounds represents a new and potentially superior method for the prevention and treatment of AD. Such mixtures are curcumin, resveratrol, quercetin, Egcgand other catagins of green tea, lycopene, lutein, zeaxanthin, blueberries, berberine, Gentiein, Hesperidine, sulforaphane, silymarin, apigenin acid, ellagic acid, vitamin C , vitamin D, tocopherols of vitamin E, melatonin, eicosapentaenoic acid and other natural compounds.
In contrast, the laboratory prepared molecules that have been developed and developed so far in clinical trials by pharmaceutical industry for the prevention and treatment of AD {monoclonal antibody for AB, breakdown proteases for precursor protein Amyloid B (AVR) and target drugs tau} have few therapeutic results significant pleiotropikes abilities and are focused on a single target.
The EGCG Catesine regulates the Alpha -secrease activity upwards while producing the neuroprotective breakdown product, The soluble Avar a . Curcumin, also Pleiotropic, in itself was likely incapable of these effects in a -secretrend, and it has been shown that curcumin (and demethoxycurcumin and Bisdemethoxycurcumin) inhibits the breakdown activity of β-seretase and Gamma -Secretrend The ability of EGCG to β-secretrend and Gamma -secretrend was less lucid.
A combination of EGCG and curcuminoids is capable of adjusting the α -secretrend upwards while at the same time it inhibits both β-secretrend and Gamma -secretrend. The mixture of three koyrkoyminis compounds, EGCG plus resveratrol seems potentially capable of achieving homeostasis between the production and clearance of AB. This is a long-time THERAPEUTIC target of the amyloid in AD, which the research community had identified for a long while, while the pharmaceutical Industry has not been able to trace it.
One problem perhaps by testing the amyloid case of AD is that the underlying process of the disease has never been adequately targeted in clinical trials with moderate results. In addition to the amyloid and tau, there is a complex, multifactorial process of the disease that includes synaptic dysfunction, oxidative stress, mitochondrial dysfunction and neurotoxicity.. The main goals of tau-related AD include a mix of natural compounds such as curcumin, resveratrol and EGCG for synaptic dysfunction, oxidative stress, mitochondrial dysfunction and neurotoxicity.
The Tau protein is associated with microtubules and is believed to help regulate the stability of neural microtubules. In Tau-pathies, {including Alzheimer’s disease} The tau is abnormally altered and incorrect, resulting in its disconnection from microtubules and the creation of pathological lesions that are characteristic for each Disease. The Tau can be compared to the train ties that stabilize a railway track using brain cells to transport food, messages and other vital load to all neurons… In Alzheimer’s, changes in tau protein cause the unstable route to the hippocampus’s neurons, the center of memory. The abnormal tau accumulates in neurons, which eventually leads to the death of these neurons. The evidence suggests that abnormal tau then spreads from cell to cell, spreading the pathological tau to the cerebral cortex.
Recent studies have shown that the abnormal hyperphosphylation of tau in the brain plays a vital role in the molecular pathogenicity of AD and neurodegeneration.
Neurogenic pathology, which is composed of abnormal superphosphorylated tau protein, associated with microtubules, is the basic alteration of the AD and its/or diseases. The density of neurogenic pathology in the cerebral cortex is correlated with the degree of dementia. The abnormal hyperphosphylation of tau causes cognitive impairment and the agglomerated tau leads to neurodegeneration and the inhibition of TAU’s abnormal hyperphosphyosis is the most rational therapeutic target in AD. The koyrkoyminis mixture, EGCG plus resveratrol targets a wide set of factors involved in the AD amyloid hypothesis, but it targets both the superphosphorylated tau, the Tau and tau oligomers Neyroϊnidiaka grids. The amyloid beta and tau form fibrin lesions which are the classic characteristics of the AD and the accumulation of toxic proteins in the conclusion leads to neurodegeneration.
Synapses {main positions for chemical communication between neurons} exposed to modified tau protein risk loss of synaptic contacts culminating with dementia. Alzheimer represents a synaptic disorder.
Oxidative damage to RNA molecules has been described in various neurological conditions such as Alzheimer’s, Parkinson, Down syndrome and dementia with Lewy bodies and amyotrophic lateral sclerosis, while the early involvement of RNA oxidation in neurodegenerative Diseases is strongly supported by a recent observation of increased oxidation of RNA in the brain of individuals with mild cognitive impairment.
Oxidative damage to mitochondrial DNA (mtDNA), a determining fact of aging, can cause or enhance mitochondrial dysfunction by favouring neurodegenerative events. This accumulation of oxidized mtDNA bases during the Aging increases the risk of sporadic AD.
The postmortem evidence of oxidative damage in the brain of patients with Alzheimer’s disease is overwhelming and suggests that oxidative stress is an early event in the disease process and can cause various adaptive responses such as Changes in the metabolism of amyloid B and activation of Kionia that respond to anxiety, lead to neuronal degeneration and pathology AD.
“The evidence shows the crucial role of AB metabolism in the challenge of oxidative stress observed in patients with AD. However, it has also been suggested that oxidative damage precedes the occurrence of clinical and pathological AD symptoms, including the deposition of amyloid-B, the formation of neuroviral mixed vessels, vascular dysfunction, metabolic syndrome and cognitive decline “.
As with amyloid, tau and synaptic dysfunction, the koyrkoyminis mixture, EGCG plus resveratrol is capable of targeting the effects of oxidative stress on brain aging and AD.
In the brain AD, the glial cells are in close correlation with amyloid B (ab) deposits. The histological examination of the AD brain as well as the studies of cell cultivation showed that the interaction of microgaloi with the fibrin of AB leads to phenotypic activation resulting in the production of Chemopine, neurotoxic cytokines and Reactive oxygen and nitrogen species that are harmful to the CNS central nervous system.
The activated Microgliia is associated with the progression of Alzheimer’s disease, as well as with many other neurodegenerative diseases of aging. Β-amyloid (AB) Deposits activate the complement system, which in turn stimulates Microgliia to release neurotoxic materials. Inflammation of the brain, characterized by increased activation of mikroglykaimias and astrocytes, increases during aging and is a key feature of neurodegenerative diseases where neuronal death and synaptic Attenuation {by amyloid-B peptide} is caused at least in part by activation of Microgaloi and astrocytes. Activation of the nervous system results in prolonged production of proinflammatory cytokines and reactive oxygen species, causing a chronic inflammatory process.
AB itself, an inducer of Microglian and Neuroneurone activation, is considered as a underlying and unitary agent in the development of AD. A vicious cycle of inflammation was formed between the accumulation of AB, activated Micrologia and Microglian inflammatory mediators, which strengthen the deposition of AB and the Neuroneurone. The curcuminoids and EGCG mixture plus resveratrol targets the factors of neuropharmacology in the aging brain and AD.
Curcumin reduces the activation of Micrologia and Astrocytopenia, the production of cytokine and it anastella the NPP- κ V, TNF- a , IL-1b in Microgliia.
EGCG significantly suppresses the expression of TNF a , of interleukin-1b, interleukin-6 and EPAGWGIMIS nitric oxide Synthase (INOS) restore levels of intracellular antioxidant NRF2 and hemi-1 OXYGENASE (Ηo-1), thus inhibiting reactive oxygen species caused by the NPP- k B.
Resveratrol inhibits the proliferation of [Oligomers] AB, the production of pro-inflammatory agents, including ROS NO [nitric oxide], ESR- a and IL1Β. The SIRT1 {agonist resveratrol} overexpression reduces THE signaling Of NF-kappab with strong neuroprotective effects.
Mitochondrial dysfunction is increased in very early stages of Alzheimer’s disease and worsens oxidative stress, which contributes to the pathology of Patients mitochondria play a vital role in cellular bioenergy, biosynthesis Of Hemi, thermogenesis, calcium homeostasis, lipid catabolism and other metabolic activities. Given the extensive role of mitochondrial in cell function, mitochondrial dysfunction plays a role in many diseases, including diabetes and Alzheimer’s disease (AD). Amyloid-B (AB) and tau cause mitochondrial lesions, a disorder that acts as a key factor in the synaptic failure and degeneration of AD. Mitochondria is a critical organ in neurons. .
Mitochondrial function and cell viability increases with curcumin.
EGCG and Luteolin were identified as the leading two mitochondrial restorative vines compounds from in vitro . The EGCG was further tested in Ninoto determine its effects ON mitochondrial brain function in model with AD. egcg treatment restored mitochondrial function rates by 50 to 85% in mitochondria isolated from the hippocampus, bark and striatum.
Resveratrol regulates mitochondrial function, the redox biology and dynamics in experimental models in vitro and in vivo. Resveratrol weakens mitochondrial damage caused by some stress factors, regulates antioxidant enzymes found in mitochondria, reducing the production of active species. Resveratrol also causes mitochondrial biogenesis, improving the bioenergetic state associated with mitochondria in Mammalian Cells.
SOURCE: J Alzheimers Dis Rep 2019
