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FOCUS: RESEARCH ON NEURODEGENERATIVE DISEASES |
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Moderate decrease in mass and volume of the human brain, probably reflecting death of brain cells, is part of the normal aging process. Since most brain and spinal cord nerve cells (neurons) are not readily regenerated, more pronounced losses, stimulated by aging, trauma or disease processes, may eventually lead to neurodegenerative diseases (NDD).
While these diseases appear to be mostly sporadic (not due to genetic mutations), mutations in various genes have been found to be associated with inherited variants of these disorders. With increased life expectancy and changing population demographics in the developed world, NDD present mounting personal, social and economic costs, and are becoming an increasingly significant cause of morbidity and mortality.
NDD may be broadly divided into two types: (1) Those causing problems with movement and; (2) Those affecting memory and/or associated with dementia. Over 30 disorders, each with different symptoms, fall into these categories. While many palliative treatments have become available, there are still no real cures for most of these progressive and debilitating conditions.
Alzheimer’s Disease (AD), the most widespread NDD, affects more than 5 million people in the United States alone: 1-2% in the general population, 5-10% among those over 65, and 20-30% of those over 80.
This year marks exactly 100 years since Dr. Alois Alzheimer, then working in Munich, published the first report on the disease now named after him. AD is characterized by the accumulation of cellular tau protein, which following abnormal phosphorylation, forms neurofibrillary tangles inside the neurons, causing aberrations in neuronal cell function, including control of memory and intellectual activity. In addition, plaque, consisting of insoluble β-amyloid (β-A) polypeptide aggregates, accumulates outside the cells, disturbing the connections between neurons and inducing massive neuronal cell death.
While its symptoms have been known and treated since ancient times, Parkinson's Disease (PD), the second most prevalent NDD, was only formally recognized by British physician James Parkinson in 1817. In the United States alone, over one million people suffer from PD, with an additional estimated three to four million cases going undiagnosed. The lesions in this disorder affect the part of the brain controlling voluntary movement, specifically destroying neurons producing dopamine (one of the neurotransmitters responsible for communication between neurons). Another NDD, Multiple Sclerosis (MS), is a chronic inflammatory condition of the central nervous system (CNS), resulting in increasing paralysis. MS affects about 400,000 people in the United States. In MS, the myelin sheath, the fatty insulation surrounding the axons (long thread-like extensions along which messages are sent from one neuron to another), is damaged. A great deal of research has recently been directed towards the prion diseases, a family of rare progressive NDD affecting humans (such as Creutzfeldt-Jakob Disease) and animals (Mad Cow G29 Disease). In these disorders, the build-up of prions, an abnormal protein, destroys the neurons. While there is no single cause or pathological mechanism for the broad range of known sporadic and hereditary NDD, abnormal interactions or processing of intracellular proteins, which may give rise to various neuro-toxic intra- or extra-cellular aggregates, are common.
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