Halting the ß-amyloid
HE asks the same question every five minutes, complains he hasn’t eaten although he just eats. Every day, while doing things for him I wipe my tears secretly. It kills me to see daddy staring at me, lost and forlorn, not knowing who I am, the apple of his eyes - wrote a reader to a newspaper editor. The writer’s father is suffering from Alzheimer’s disease.
Alzheimer’s disease (AD) is a neurodegenerative disease, clinically characterised by a progressive decline in memory and cognitive function. The patient’s short-term memory gets shorter each day and they will forget almost immediately what they have asked or what they just did. They will pose simple questions like if they have eaten although they eat only minutes ago. Pitifully, AD not only affects the patient, it also does the caregivers. It takes a caregiver an extra measure of courage and patience to handle them.
AD inevitably leads to death due to various complications. In the western countries, AD is the fourth leading cause of death after heart diseases, cancer and stroke. Sadly, it is estimated 17 to 25 million of the world’s population are currently affected by AD, and the number is rising as we live longer. At the age of 65 years, an estimated 3% of the human population are affected by the disease and by the age of 85 years, the prevalence reaches up to 50%. The United Nations (UN) population projections estimate the number of people older than 80 years will be a staggering 370 million by year 2050, thus more than 100 million people aged over 85 years old will suffer from AD in the next 40 years.
Likewise in Malaysia, the prevalence estimate for AD in 2006 was 63,000 out of 23.4 million total population and the estimate for total societal cost of dementia which includes direct costs and informal care may rise to US$511 million. The number of sufferers is projected to 126,800 and 453,900 in 2020 and 2050 respectively.
Despite various efforts aimed at elucidating the aetiology of AD, there is still no effective treatment available to halt its progress. Approved drugs to treat AD, cholinesterase inhibitors and memantine, only help to treat the symptoms related to the disease. These drugs do not address the fundamental cause of the disease. However our scientists see that if we could develop drugs to treat its root, there will be a ray of hope to alleviate this frightening disease.
Abu Bakar Abdul Majeed hypothesized that to hit its roots, we need to study the ß-amyloid (Aß) plaque in the brain of AD patients. Aß is formed by an alternative cleavage of the amyloid precursor protein (APP) by the ß-site of APP cleaving enzyme (BACE1, also known as ß-secretase). Though Aß occurs in all individuals, in AD patients, it becomes screwed up hence disturbs their neuronal transmission. Hence, in this sense, to eliminate Aß, we need to give them drug that inhibits BACE1. This may help alleviate or prevent AD.
Hence, Abu Bakar, helped by his team at the Brain Research Laboratory, Faculty of Pharmacy, is currently studying to halt the ß-amyloid production in a diseased brain. To do so, they attempt to inhibit BACE1 that will reduce or virtually halt the ß-amyloid production in the AD patients’ brain. Supported by UiTM and various research grants from MOSTI, the group has tested over 300 extracts obtained from Malaysian endophytes for BACE1 inhibitory activity.
An endophyte is a microorganism that lives within a plant for at least a part of its life without causing apparent disease to its host. It is often a bacterium or fungus that produces metabolites which are not harmful to its host and could be useful to mankind. A large number of endophytes and its metabolites have still not been characterized to date and they are currently viewed as an outstanding source of bioactive natural products.
In this team’s study, out of the 385 endophytic extracts tested for BACE1 inhibitory extract, 14% showed inhibitory activity above 90%. The team has been working closely in collaboration with the University of Canterbury at Christchurch in New Zealand to determine and elucidate the structure of pure compounds found in the potent endophytic extracts responsible for the inhibitory activity of BACE1. In particular, the group has found one unknown compound coded as HAB16FC79 which has a very effective IC50 value of 0.2 μM. HAB16FC79 has a small enough molecular weight capable to cross the blood-brain barrier and work is still in progress elucidating its structure and other neuroprotective properties.
Information contacts:
Abu Bakar Abdul Majeed1
Richard Muhammad Johari James2
Jean-Frédéric Faizal Weber2
Kalavathy Ramasamy2
Vasudevan Mani2
Nur Suraya Adina Suratman3
Lim Siong Meng3
Nurul Aqmal Mohd Hazalin3
Azzeme Harun3
Nurhuda Musa3
John Blunt3
Tony Cole3
Murray Munro3
Lin Sun3
1Research Management Institute
UiTM Shah Alam
2Faculty of Pharmacy
UiTM Puncak Alam
3University of Canterbury
New Zealand
abubakar@salam.uitm.edu.my
Making up the brain
MIND fleets. Brain pulses. The merging of Mind and Brain (or brain and mind?) makes up their mystique, fostering our curiosity in them.
The Quran, the Bible and other great teachings encourage Man to discover the mysteries of God, thus indeed it is - the 2000-year old Shroud of Turin examination shines the mystiques and the power of human inquisitiveness, woven in the minds and brains of scientists.
The examination resonates the Verses of Al-Baqarah, the conversation between God and His Angels at the time of human creation about the difference between having wisdom and not having one.
The Verse says “Behold, thy Lord says to the angels: ‘I will create a voce-gerent on earth’. The angel says: Wilt Thou place therein one who will make mischief herein and shed blood? Whilst we celebrate thy praises and glorify Thy holy (name)?’ God replied: ‘I know what ye know not.’ And He taught Adam the nature of all things; then He placed them before the angels and said: Tell Me the nature of these if ye are right’. They said: ‘glory to Thee, of knowledge. We have none save what Thou hast taught us: in truth it is Thou who are perfect in knowledge and wisdom’. God said: ‘O Adam! Tell them their natures’. When Adam had told them, God said: Did I not tell you that I know the secrets of heaven and earth, and I know what ye reveal and what ye conceal’?”
In the 33 A.D. Shroud of Turin, in 2009 A.D, the brains in nine fields of knowledge: theology, textile, history, DNA, carbon dating, flora and fauna, photography, 3D imaging, and lights were brought together. The scientists gathered at the Vatican, permitted to study the holy shroud in five days. They examined the linen for 122 hours, day and night, yet the mind and the brains of theology and science, still failed to demystify the Shroud of Turin if it was indeed wrapping the body of Jesus. It could only determine that the man whose body wrapped in the shroud was scourged violently, crucified cruelly and stabbed in the rib severely. The team could even bring the man’s face almost alive in a 3D dimension, but failed to determine if the man was really Jesus. Is there a Being beyond us, far beyond the brain, the mind and the science?
However, research, such as the research of the Shroud of Turin, and other form of research, seems to point that hitherto the unbridgeable gap between the psychical and the mental world of brain, mind and science is slowly narrowing.
The brain is a grey matter, carrying its own mystic and enigma, establishing the very being of a human being. Scientists call it the most mysterious organ of the human body. Thus much has been argued about the brain. However, as though it is not enough, out of this mystery, arises an even more mystifying entity - the mind. They have given rise to heated debates on the ultimate question: is mind and brain one, or are they distinctively separate? The mind is elusive, fleeting every second, shown in thoughts, languages, and perceptions, so does directing feelings, emotions and recalls.
Neuro-physiologists describe the brain as just a 1.4 kg grey matter containing approximately 100 billion nerve cells. The nerve cells are also called neurons. The neurons communicate with one another, busily sending electrical signals along the neuronal body of axons and dendrites. Further, trillions of nerve junctions or synapses link these neurons together. Chemicals in the synapses or neurotransmitters, help bridge the neurons. Does this anatomy follow the order of the mind to make up a mind? Undoubtedly, the brain with its mind or faculty of reason does. Thus man rests well above the rest of God’s creatures.
Animal, too, think and feel. Thus they do have brains. Do they not have mind? A mother monkey will hug her dead baby for days before she let it go, thus hunters are warned not to shoot mother monkeys.
Early neuroscientist, Andreas Vesalius (1514-1564 A.D.), a native of Brussels, in his landmark publication On the Workings of the Human Body, indicated that the cavities of the human brain were not different from those of other mammals. However, they do not have similar reasoning powers. Thus Adam’s ability to learn, understand and remember positions him as a superior being, despite being the latest addition to God’s creations.
Vesalius further wrote: ‘all our contemporaries, so far as I can understand them, deny to apes, dogs, horses, sheep, cattle, and other animals the main powers of the Reigning Soul – not to speak of other powers – and attribute to a man alone the faculty of reasoning: and ascribe this faculty in equal degree to all men. And yet we clearly see in dissecting that men do not excel those animals by possessing any special cavity in the brain. Not only is the number of ventricles the same, but also all other things in the brain are similar, except only in size and in complete consonance of the parts for virtue.”
Despite this anatomical finding, in many ways the brain power of animals is rather limited. But man may, if he wishes, make use of his brain to the maximum capacity, performing important functions, maintaining proper balance or homeostasis of the body. A man’s brain, too, if he wishes, will follow his mind. If the mind decides to kill, the brain will follow, moving the body towards the killing. If the mind decides to be kind, the brain will steer the body towards cooking and bringing the food to the poor, for example. The mind needs controlling, thus there emerge education, teachers, and wisdom. Prophets and religions revealed. Does the mind control the world? If only the good mind does, the man wrapped in the Shroud of Turin would not be whipped to death; and if only the bad do, there will not be civilization.
However, the mind will not work if not for more than 50 different neurotransmitters of acetylcholine, noradneraline, dopamine and serotonin in the brain. Nor does the mind work without that large surface of the brain, despite its small size. The surface is convoluted to enhance the size of effective area, necessary for efficient handling of a huge amount of information received by the brain every second, either from inside or outside the body.
Each site of the brain surface constantly receives and processes specific information. Thus the sites for visual and auditory input are separated despite we see and hear simultaneously. We are able to do both as both sites communicate extensively via connecting neurons. The brain’s ability to process information is unsurpassed by any other machines, not even by the best computers of the day. In fact, despite the success of computer builders to simulate brain-processing strategies as the simultaneous parallels and distribute processing, computers are still far to supersede the brain’s efficiency.
The computer may be faster, but the brain is much more insightful and prudent. Thus it is not surprising to find that the brain can efficiently perform numerous complex tasks like thinking, memorizing, counting, listening, speaking, planning, making decisions and dealing with emotions. A computer will not be able to do all this in one system. Placing brain to computers, by and large, brains are agile, computers rudimentary.
The brain is the center of control of most of the internal workings of the human body. The lower region of the brain, the medulla oblongata, controls the beating of the heart, as well as the rhythmic movement of respirations. The brain triggers hormonal release thus controlling our growth, metabolism, sexual maturity and mood.
The ability of the brain to control the functioning of the various organs and systems of the body is made possible via a precise feedback mechanism. As a consequence of being the nerve center of the body, injury to the brain will result in serious handicap to the individual. Consequently, brain non-function is akin to death – brain death.
Thus God iterates the marvels of the brain in His word aql, the evolvement of the mind. The root word aql does not occur in the noun form at all in the Quran but only in the verb form, suggesting it is a dynamic application.
In the verses of the Quran, the derivatives of the word aql are used to represent activities that are performed, or need to be performed, or activities not performed despite their indispensability. Also in the Quran, activities pertaining to the mind are always referred to in a positive sense. There is no suggestion whatsoever that using the mind would lead to undesirable consequences.
The capability of the brain and mind is almost limitless. Man must not let His command go unheeded - that we have to strive, discover, and move on.
Information contacts:
Abu Bakar Abdul Majeed
Megawati Omar
Research Management Institute
UiTM Shah Alam
abubakar@salam.uitm.edu.my
megawati@salam.uitm.edu.my
