APPROACHES TO MANAGE ALZHEIMER DISEASESS

COMPENDIUM ON VARIOUS APPROACHES TO MANAGE ALZHEIMER DISEASE: Alzheimer’s disease can be defined as a progressive neurodegenerative disease in which degeneration of the brain and neurons takes place, and eventually, as time progresses, these cells die.
SIGNS AND SYMPTOMS OF ALZHEIMER’S DISEASEPATHOPHYSIOLOGY OF ALZHEIMER’S DISEASE, Creation of neurofibroblast-like structures, Alzheimer's disease experimental models, Alzheimer's disease types, and Alzheimer's disease diagnosis
Alzheimer's disease treatment strategies that combine synthetic and natural plant therapies include:

1. INSTITUTE: UIPS DEPARTMENT:PHARMACY TOPIC - COMPENDIUM ON VARIOUS APPROACHES TO MANAGE ALZHEIMER DISEASE By – Muskaan

2. What is Alzeheimer Alzheimer’s disease can be defined as a progressive neurodegenerative disease in which degeneration of brain and neurons takes place and eventually as the time progresses these cells die. Alzheimer’s disease is the most common cause of dementia in which means chronic or persistent disorders of brain processes and it is identified by memory disorders, personality changes and impaired reasoning.

3. SIGNS AND SYMPTOMS OF ALZHEIMER’S DISEASE Memory loss affecting daily activities, and difficulty in performing daily activities. Difficulty with familiar tasks. Difficulties with problem-solving Trouble with speech or writing Becoming disoriented about times or places Decreased judgment Decreased personal hygiene Drastic Mood and personality changes Mental and emotional withdrawal from friends, family, and community.

4. PATHOPHYSIOLOGY OF ALZHEIMER’S DISEASE: Although the cause of Alzheimer’s disease isn’t completely understood but two pressure players that are often cited in its progression are known as plaques and tangles. FORMATION OF PLAQUES: Here we have got the cell membrane of a neuron in the brain in the membrane we have a molecule known as amyloid precursor protein or (APP) one end of this molecule is inside the cell and the other end is outside the cell. Although the exact role of this molecule isn’t completely understood but it is thought that it helps neurons to grow and repair itself after an injury. Since APP’s is a protein and just like other proteins it gets consumed and over time it gets broken down and recycled Normally, it gets chopped up by an enzyme known as alpha secretase along with the help of gamma secretase This chopped up peptide is soluble and gets recycled easily    

5. Now the main problem arises when this process is done by beta secretase instead of alpha secretase and along with gamma secretase and when this happens the left-over chopped protein by these two enzymes is not soluble and forms a monomer called Beta-Amyloid protein. These monomers tend to be more chemically “sticky” and bond together just outside the neurons and together many of these forms beta-amyloid plaques forming a clot of these monomers. These plaques can potentially get between the neurons which can get in the way of neuron to neuron communication. If the brain cells can’t signal and relay information then brain functions like memory can be seriously impaired. It’s also thought that these plaques can start up immune responses and cause inflammation making it auto-immune disease. Beta amyloid plaque can also deposit around blood vessels in the brain called amyloid angiopathy which he gets the walls of the blood vessels and increases the risk of average or rupture and blood loss.      

6. FORMATION OF NEUROFIBRILLARY TANGLES: Another big part of Alzheimer’s disease are tangles and these are actually found inside the cell, as opposed to the beta-amyloid plaques.   Just like other cells neurons are held together by their cytoskeleton which is partly made up of microtubules these track like structures essentially act like a minecart shipping nutrients and molecules along with the length of the cell.   A special protein called tau protein don’t break apart kind of like railway. Although again, the exact role Beta-Amyloid plaque is not completely understood it’s though that the beta amyloid plaque build-up initiates pathways inside the neuron that leads to activation of kinase, an enzyme that transfers phosphate groups to the tau protein.

7. Neurons with tangles and non-functioning microtubules can’t signal as well and sometimes end up undergoing apoptosis or programmed cell death.   As neurons die, large scale changes start to take place in the brain, for one, the brain atrophy takes place in which the brain shrinks and the gyri gets narrower which are the characteristic ridges of the brain.   As those get narrower, the sulci, which are the grooves between the gyri, gets wider with atrophy the ventricles, fluid filled cavities in the brain gets larger.  

8. TYPES OF ALZHEIMER’S DISEASE: Alzheimer’s disease can be classified into two groups : Sporadic Familial

9. DIAGNOSIS OF ALZHEIMER’S DISEASE: Diagnosis of Alzheimer’s disease is really tough because the only way to definitely show that a person had Alzheimer’s is by performing a brain biopsy after autopsy (Death). Alzheimer’s diagnostic tests:   There’s no particular diagnostic test for Alzheimer’s disease. However, mental, physical, neurological, and imaging tests can help your doctor reach a diagnosis. The doctor may also order brain imaging studies. These studies, which will create pictures of your brain, can include: Magnetic resonance imaging (MRI) scan: MRIs can help pick up key markers, such as inflammation, bleeding, and structural issues. Computed tomography (CT) scan: CT scans take X-ray images, which can help your doctor look for abnormal characteristics in your brain and any other abnormalities.   Other tests your doctor may do include blood tests to check for genes that may indicate you have a higher risk of Alzheimer’s disease.

10. Alzheimer’s Disease Experimental Models

11. Natural Plants used in Alzheimer’s disease Natural compounds contain many phytoconstituents which are utilized as raw materials to treat different diseases. Various metabolites and active compounds from plants are utilized in pharmaceutical industries for production of drugs. Plus, medicinal plants gain wide acceptance because of fewer side effects compared to synthetics one.   Moringa oleifera Moringa oleifera commonly known as Drumstick tree, Horse Reddish Tree, Bean oil Tree belongs to the family Moringaceae. Pharmacological Activities Anti-inflammatory activities in leaves extract, Neuropharmacological activities, Antioxidant, Anticancer, Cardiovascular activity (reduced cholesterol level, Antihypertensive, reduced chronotropic and ionotropic actions), Anti-asthmatic (due to bronchodilation, anti-inflammatory activity), Antidiabetic and many more ( 3,4 )

12. Centella asiatica Plant description – Centella asiatica is a medicinal plant commonly known as Gotu Kola or Mandukaparni or jalbrahmi. belongs to the family Umbellifere  ( Apiceae ) Pharmacological activities This plant has broad pharmacological activities such as Wound healing (ointment, cream, gel), It possess some CNS effects such as Sedative, anxiolytic, tranquilizer and intelligence promoting property Withania Somnifera Plant description – It is very divine drug of Ayurveda commonly known as Ashwagandha belongs to the family Solanaceae. Pharmacological Uses - Antimicrobial and antifungal activities Antidot , Anti-inflammatory, Anti analgesic anti-arthritic neuroprotective, ant ischemic, anti-Parkinson’s, antiepileptic, anxiolytic, antidepression

13. Bacopa monnieri Plant description – This plant is commonly known as Brahmi belongs to the family Plantaginaceae Pharmacological activities anticonvulsant, antidepressant, anxiolytic, analgesic, anti-inflammatory, antioxidant, antimicrobial, antiulcerogenic, anti-Helicobacter pylori, apoptogenic, antineoplastic, bronchodilator, hepatoprotective and immunostimulatory Convolvulus pluricaulis Plant description : Convolvulus pluricaulis commonly known as Shankhapushpi that seems like morning glory Convolvulaceae Pharmacological activities Antioxidant (Ascorbic acid) antidepressant, anxiolytic, anticonvulsant

14. Curcuma longa Plant description Curcuma longa (C. longa) Linn commonly known as turmeric belonging to the family Zingiberaceae Pharmacological Activities - Antioxidant, Anti-inflammatory, Anti- amyloid, Cholesterol lowering property, Neuroprotective, Carminative, Diuretic, Anti-diabetic, Analgesic, Insecticidal Eclipta Species Plant description – Eclipta species commonly known as Bringhraj belongs to the family Asteraceae. Pharmacological Effects Antihemorrhagic activity, Cardiovascular effect, antihepatotoxic agent, anti-inflammatory agent, Antivenomous effect, Antimicrobial

15. Clitoria ternatea Plant description - Clitoria ternatea belongs to family Fabaceae commonly called “butterfly”. Pharmacological effect - Nootropic, anticonvulsant, antidepressant, antianxiety, antistressor, antioxidant, anti-inflammatory, antihyperlipidemic, antidiabetic, antiasthma tic, analgesic, immunomodulatory, cytotoxicity, platelet aggregation inhibitory, antimicrobial, gastroprotective and hepatoprotective Celastrus paniculatus Plant description - Celastrus paniculatus (C. paniculatus) commonly known as Jyotismati belongs to the family Celastraceae. Pharmacological activities - anti -inflammatory, antioxidant, anti-infertility, antiarthritic, wound healing, hypolipidemic, neuroprotective

16. Desmodium gangeticum Plant description - Desmodium gangeticum (D. gangeticum) commonly known as Salpani belonging to the family Fabaceae. Pharmacological activities - Antinociceptive, cardioprotective, antileishmanial, immunomodulatory, antioxidant, anti-inflammatory and ant amnesic and hepatoprotective.

17. Synthetic treatment approach to treat Alzheimer’s Disease: Introduction There is no cure for Alzheimer’s disease, but available medications temporarily slow the worsening of dementia symptoms and help with behavioural problems that may appear during the course of the disease. Synthetic Drugs for AD: Phenserine is a phenyl carbamate derivative of physostigmine with long acting and pseudo-irreversible + AChE inhibitory activity

18. RIVASTIGMINE Rivastigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. TACRINE I n Alzheimer's disease, many chemical changes take place in the brain. One of the earliest and biggest changes is that there is less of a chemical messenger called acetylcholine ( ACh ). ACh helps the brain to work properly. Tacrine slows the breakdown of ACh , so it can build up and have a greater effect. However, as Alzheimer's disease gets worse, there will be less and less ACh .

19. DONEPEZIL: Donepezil is indicated for the symptomatic treatment of mild to moderate Alzheimer’s disease. It is a specific and reversible inhibitor of acetylcholinesterase by increasing levels of available acetylcholine. MEMANTINE: Memantine is a prescription drug. It comes in three forms: immediate-release tablet, oral solution, and extended-release capsule

20. NICERGOLINE: Nicergoline is a potent vasodilator that improves brain blood flow on the cerebral level it prompts a lowering of vascular resistance, an increase in arterial flow and stimulates the use of oxygen and glucose METRIFONATE: Metrifonate is a long-acting irreversible cholinesterase inhibitor, originally used to treat schistosomiasis. Its potential to enhance central nervous system cholinergic.