Alzheimer’s disease is a progressive, irreversible form of brain disorder (dementia). It is caused due to deposition of proteins like tau and amyloid in and around brain cells. It is responsible for brain cell degeneration and induces a gradual deterioration in the ability of an individual to function independently. Forgetting the recent conversations or events is the early symptoms of Alzheimer's disease. The level of acetylcholine, a neurotransmitter is found lower in Alzheimer’s disease patient. This disease is usually found in the people of older age groups. Alzheimer’s disease is named after Dr. Alois Alzheimer after observing the brain tissue of a woman.
Causes of Alzheimer’s disease
Age, family history, genetics, unhealthy diet, obesity, depression, sedentary life style, consumption of alcohol and smoking etc. are the factors that increase the risk of Alzheimer’s disease. Oxidative stress causes elevation of intracellular reactive oxygen species (ROS). Excess production of ROS shows negative impact on cell functioning. Mitochondria and plasma membrane, two cellular organelles act as major source of ROS. Alternation of electron transport chain in mitochondria and increased free fatty acids in metabolic disorders leads to generation of ROS which react with oxygen molecules and produce superoxide radical. This is responsible for oxidative stress and formation of toxic compounds like peroxides and alcohols. Further, oxidative stress on the nervous tissue can significantly damage the brain. Free radicals are responsible for brain protein oxidation and influence the activity of different enzymes such as glutamine synthetase and creatine kinase, which play a critical role in proper neuron functioning. ROS contributes to reactive nitrogen species (RNS) growth. Superoxide ions react with nitric oxide (NO) and form more effective oxidants – peroxynitrite (ONOO-), thus connecting oxidative stress closely to nitrosative stress. Reports suggest that NOS (nitric oxide synthase) is triggered by cells exposed to mild oxidative stress (such as ionizing radiation or low H2O2 concentrations).
Management of Alzheimer’s disease (AD)
Intake of antioxidant molecule is the best way to achieving normal physiological functioning in the brain. Naturally occurring polyphenolic compounds are of greater interest to scientists worldwide due to their beneficial effects on a wide range of pathophysiological disorders, including neurodegenerative diseases. Cells are protected against the damage caused by ROS by both enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic antioxidants (glutathione, vitamin C and vitamin E) body antioxidant systems. Nutraceuticals among them are a distinct group of natural bioactive molecules found in the regular diet of humans. When these nutraceuticals are properly consumed, some protective effect against several pathophysiological conditions can be demonstrated. The compounds of nutraceuticals such as curcumin, mangiferin, genistein, resveratrol, arjunolic acid, taurine and vitamins have been shown to be multipotent therapeutic molecules with a beneficial effect on AD.
Caffeic acid is present in coffee, tea, different fruits and vegetables. It shows different pharmaceutical efficiencies, like anti-inflammatory, anti-cancer, anti-viral, anti-hypertensive, antithrombosis, anti-fibrosis activities and others. The oral administration of caffeic acid is shown to restore spatial, mental and memory functions in an Alzheimer's affected mouse model. Caffeic acid can control the production of lipid peroxidation and nitric oxide in the kidney, liver and brain effectively.
Berberine (bitter-tasting) is yellow coloured plant alkaloid obtained from stem, bark, roots and rhizomes of many plants like goldenseal (Hydrastis canadensis), Oregon grape (Berberis aquifolium), coptis or golden thread (Coptis chinensis), tree turmeric (Berberis aristata) and barberry (Berberis vulgaris). It has neuroprotective and neurotrophic properties. Recent studies indicate that berberine reduces the production of amyloid and inhibits expression of NOX and COX.
Silymarin is extracted from the herb milk thistle and its silibinin, a flavonoid molecule is the main component present in it. This compound contains anti-inflammatory and antioxidative properties. It is also reported to be effective against ethanol-induced brain injury, and lipopolysaccharide mediated neurotoxicity. On treatment of Alzheimer’s disease affected mouse model with silymarin extract improves its memory function. Administration of silymarin extract also decreases the deposition of amyloid and suppresses Amyloid Precursor Protein gene expression in the brain. Silymarin is found to slow down the progression of neurodegeneration in Alzheimer’s disease affected mouse model and enhances resistance to oxidative stress. Silibinin reduces learning and memory deficits. The activation of neurogenesis, gliogenesis and synaptic defense is also found.
Icariin is a natural product from Epimedium herba, a Chinese plant. It improves the storage of
memory and the ability to learn.
Curcumin is a polyphenolic, non-toxic compound extracted from a south Asian herb, Curcuma Longa (Turmeric). It is regarded as a therapeutic food from ancient time. It possesses anticancer, antidiabetic and antioxidant effects. Several in vitro studies have reported the potential of curcumin to reduce the aggregation of amyloid peptides in the neural tissue. It is proved that oral administration of curcumin can reduce the deposition and oligomerisation of amyloid peptide along with the phosphorylation of the tau protein and improve cognition and behavioural impairment in experimental animal. Metal ions such as Cu (II) and Zn (II), increase aggregation of amyloid peptide and have a critical role in the pathogenesis of Alzheimer’s disease. Different studies suggest that curcumin have ability to bind these metal ions and provide neuroprotective property. curcumin can induce a major structural changes in the amyloid protein by modifying the amino acid sequences in a salt bridge region and the c-terminus of the protein. Another study revealed that curcumin can directly inhibit the production of Amyloid peptides and inhibit neurodegeneration. It is easily accessible and economical by which the person affected by Alzheimer’s disease can afford it.
Resveratrol is a phytoalexin molecule and is polyphenolic in nature. It is most abundantly found in the seeds and skin of grapes. It is regarded as a prophylactic natural compound. It is antioxidant in nature ffective against diabetes, cancer, and inflammation, cardio-protective, reno-protective and hepato-protective, anti-neurodegenerative. Resveratrol at 200 mg/kg body weight is found to reduce oxidative stress and neuro inflammation. It reduces aggregation of alkaloid and tau peptide either directly or indirectly.
Genistein is isoflavonoids found in leguminous plants especially in the soy plants. Genistein possess several prophylactic health effects against different types of pathophysiological conditions like cancer, cardiovascular diseases, diabetes etc. Due to presence of several phenolic moieties in its structure, genistein contain good anti-oxidant property. Some studies have revealed that administration of this bioactive molecule is beneficial in the improvement of learning and memory. It also reduces formation of amyloid peptide and the level of intracellular ROS and inhibits mitochondrial dysfunction and simultaneous elevation of the intracellular antioxidant enzymes. Genistein can inhibit the hyperphsphorylation of tau protein. One of the major advantages in using genistein over the contemporary practice of using hormone replacement therapy to combat Alzheimer’s disease in postmenopausal women is that, this polyphenolic molecule can act as an oestrogen agonist and it has a neuroprotective effect, which does not interfere with the proliferative pathways in the uterine endometrial cells. However, there is no report yet, describing the applications of genistein for the treatment of Alzheimer’s disease, in clinical studies and can be expected in near future because of its promising pre-clinical data.