Treatment for Alzheimer disease:
Modern medicine and well established healthcare system prolonged the average length of the human life. Old age is associated with numerous neurodegenerative disorders; most typical is Alzheimer’s disease. Risk for developing Alzheimer’s disease is increasing with the age. It is estimated that 10% of people over the age of 65, and 50% of those over 85 suffers from Alzheimer’s disease. Most cases develop sporadically and just 1-5 % of Alzheimer’s cases are genetically inherited.
Alzheimer’s disorder is first described in 1906. Post mortem brain analysis and blood markers provided more information on this pathological brain disorder over the past 100 years, but exact trigger for the disease and successful treatment method are still lacking. Alzheimer’s disorder is characterized by brain shrinkage, loss of neuronal connections and disrupted blood brain barrier. Several theories about disorder genesis exist: cholinergic theory, where lack of acetylcholine triggers disorder, herpes simplex virus induced disorder, age related impaired myeline breakage or oxidative stress as a cause of neurodegeneration…Most probable are ones associated with altered metabolism of amyloid precursor protein and tau protein. Amyloid precursor protein is building part of neuronal synapses and essential ingredient of various cell membranes in the body. Proteolitic degradation of amyloid precursor protein results in formation of the fibrial protein - beta amiloid that is found in brain plaques, typical for Alzheimer’s disorder. Beta amiloid alters calcium ion homeostasis (resulting in apoptosis), inhibits enzymatic activity and prevents glucose utilization. Tau protein is essential for development of neuronal polarity; it promotes neuronal microtubule assembly and enhances axonal dynamics. When tau protein is hyperphosphorilated, it becomes insoluble and forms inclusions known as neurofibrillary tangles. Those tangles are associated with neuronal degeneration. Alzheimer’s disease can be diagnosed using couple of techniques: brain imaging (computed tomography or magnetic imaging), through neuropsychological tests or by blood analysis (couple known markers exist). Current treatments are focused on the main attributes of Alzheimer’s disease: dementia (memory loss), depression and cognitive impairments. Medication used is just slowing down the progression of neurodegeneration but it can’t prevent disease. Typical mechanism of action is focused on proteolysis of amyloid precursor protein; latest drugs could prevent proteolysis or bind to already formed beta amyloid prior its aggregation and eliminate it. Other drugs affect distribution of beta amiloid through the brain or decrease the rate of neuroinflammation. Alzheimer’s disease is one of the most common neurodegenerative disorders associated with old age and one of the most expensive to be treated because patients demand special care due to physically, physiologically and socially altered behavior.
Latest discoveries in the stem cells field could move Alzheimer’s treatment in completely new direction. Scientists from the University Of California, Irvine developed new line of stem cells - choroid plexus epithelial cells (CPECs) using human and mouse embryonic cells. Choroid plexus is part of the brain ventricles where cerebrospinal fluid is produced. This liquid is important for cleaning the waste products and metabolites that could damage the brain function. 500 milliliters of cerebrospinal fluid is produced each day, and it is renewed 4 times a day to ensure efficient detoxification of the neuronal tissue. CPECs are forming important blood - cerebrospinal fluid barrier. Neurodegenerative disorders are associated with dysfunctional CPECs and inefficient removal of the waste material (like beta amiloid) from the cerebrospinal fluid. Scientists were familiar with the role and importance of CPECs cells, but until now they couldn’t find the way to produce those cells in vitro. Embryonic cells are pluripotent and different transcription factors determine their cellular faith (direction of their differentiation). After discovering that brain morphogenic factor 4 (BMF4) is responsible for differentiation of the neuronal progenitor cells into CPECs, researchers applied BMF4 to produce sufficient amount of CPECs. Both human and mouse neuronal progenitor cells used in the experiment matured successfully into CPECs after BMF4 was applied. Developed CPECs act just like naturally produced cells; they could integrate in choroid plexus epithelium and form secretory vesicles. Neurological disorders associated with the accumulation of the peptides, proteins and other metabolites that alter normal function of the brain could be treated using CPECs. Scientists are hoping that this approach will be especially helpful in Alzheimer’s and Huntington’s disease as well in treatment of pediatric neurodegenerative disorders.
Modern medicine and well established healthcare system prolonged the average length of the human life. Old age is associated with numerous neurodegenerative disorders; most typical is Alzheimer’s disease. Risk for developing Alzheimer’s disease is increasing with the age. It is estimated that 10% of people over the age of 65, and 50% of those over 85 suffers from Alzheimer’s disease. Most cases develop sporadically and just 1-5 % of Alzheimer’s cases are genetically inherited.
Alzheimer’s disorder is first described in 1906. Post mortem brain analysis and blood markers provided more information on this pathological brain disorder over the past 100 years, but exact trigger for the disease and successful treatment method are still lacking. Alzheimer’s disorder is characterized by brain shrinkage, loss of neuronal connections and disrupted blood brain barrier. Several theories about disorder genesis exist: cholinergic theory, where lack of acetylcholine triggers disorder, herpes simplex virus induced disorder, age related impaired myeline breakage or oxidative stress as a cause of neurodegeneration…Most probable are ones associated with altered metabolism of amyloid precursor protein and tau protein. Amyloid precursor protein is building part of neuronal synapses and essential ingredient of various cell membranes in the body. Proteolitic degradation of amyloid precursor protein results in formation of the fibrial protein - beta amiloid that is found in brain plaques, typical for Alzheimer’s disorder. Beta amiloid alters calcium ion homeostasis (resulting in apoptosis), inhibits enzymatic activity and prevents glucose utilization. Tau protein is essential for development of neuronal polarity; it promotes neuronal microtubule assembly and enhances axonal dynamics. When tau protein is hyperphosphorilated, it becomes insoluble and forms inclusions known as neurofibrillary tangles. Those tangles are associated with neuronal degeneration. Alzheimer’s disease can be diagnosed using couple of techniques: brain imaging (computed tomography or magnetic imaging), through neuropsychological tests or by blood analysis (couple known markers exist). Current treatments are focused on the main attributes of Alzheimer’s disease: dementia (memory loss), depression and cognitive impairments. Medication used is just slowing down the progression of neurodegeneration but it can’t prevent disease. Typical mechanism of action is focused on proteolysis of amyloid precursor protein; latest drugs could prevent proteolysis or bind to already formed beta amyloid prior its aggregation and eliminate it. Other drugs affect distribution of beta amiloid through the brain or decrease the rate of neuroinflammation. Alzheimer’s disease is one of the most common neurodegenerative disorders associated with old age and one of the most expensive to be treated because patients demand special care due to physically, physiologically and socially altered behavior.
Latest discoveries in the stem cells field could move Alzheimer’s treatment in completely new direction. Scientists from the University Of California, Irvine developed new line of stem cells - choroid plexus epithelial cells (CPECs) using human and mouse embryonic cells. Choroid plexus is part of the brain ventricles where cerebrospinal fluid is produced. This liquid is important for cleaning the waste products and metabolites that could damage the brain function. 500 milliliters of cerebrospinal fluid is produced each day, and it is renewed 4 times a day to ensure efficient detoxification of the neuronal tissue. CPECs are forming important blood - cerebrospinal fluid barrier. Neurodegenerative disorders are associated with dysfunctional CPECs and inefficient removal of the waste material (like beta amiloid) from the cerebrospinal fluid. Scientists were familiar with the role and importance of CPECs cells, but until now they couldn’t find the way to produce those cells in vitro. Embryonic cells are pluripotent and different transcription factors determine their cellular faith (direction of their differentiation). After discovering that brain morphogenic factor 4 (BMF4) is responsible for differentiation of the neuronal progenitor cells into CPECs, researchers applied BMF4 to produce sufficient amount of CPECs. Both human and mouse neuronal progenitor cells used in the experiment matured successfully into CPECs after BMF4 was applied. Developed CPECs act just like naturally produced cells; they could integrate in choroid plexus epithelium and form secretory vesicles. Neurological disorders associated with the accumulation of the peptides, proteins and other metabolites that alter normal function of the brain could be treated using CPECs. Scientists are hoping that this approach will be especially helpful in Alzheimer’s and Huntington’s disease as well in treatment of pediatric neurodegenerative disorders.