The Human Brain : From Neurone to Nervous System

NEURODEGENERATION


  1. Neurodegenerative Diseases are diseases that result in the progressive death of neurones, and include Alzheimer's, Huntington's and Parkinson's diseases, Motoneurone disease and others.

  2. They are characterised by the presence of intracellular inclusion bodies, including
    • Lewy bodies,
    • neurofibrillary tangles,
    • the intranuclear inclusion bodies of Huntington's Disease.

  3. In Alzheimer's disease there are also extracellular accumulations of beta amyloid.
    Dementia with Lewy bodies (DLB) is a type of dementia that shares symptoms with both Alzheimer's disease and Parkinson's disease.
    Chronic repeated trauma to the brain, as occurs in some sports, also results in abnormal intracellular protein aggregates. Dementia is common in all these conditions.

  4. Misfolded protein aggregates appear to be an intrinsic part of the pathology of beta-amyloid and Lewy Bodies. Two proteins, Amyloid Precursor Protein and Synuclein Cells are present in normal cells, but are involved in the formation of beta-Amyloid and Lewy Bodies by abnormal folding of their protein chains.

  5. In nerve cells, the mechanism for handling old and abnormal proteins depends on retrograde axoplasmic transport, and misfolded proteins are transported to a peri-nuclear location, the site where Lewy bodies develop in neurodegenerative disorders such as Parkinson's Disease. If retrograde axoplasmic transport fails, misfolded proteins accumulate , and this may be the mechanism for formation of neurofibrillary tangles

  6. Some proteins, such as beta-amyloid and synuclein, accumulate in parts of the brain. While a number of pathophysiological processes contribute to the development of these conditions, it is known that normal neurotubules have an important role in the clearance of beta-amyloid from axons.

  7. Studies of animals with mad cow disease (bovine spongiform encephalopathy) have led to a concept of prion disease, in which the presence of an abnormal misfolded protein can cause normal proteins, synthesised by the neurone, to adopt an abnormal structure, which then accumulates and causes neurodegeneration. This mechanism may operate more generally in the formation of abnormal protein aggregates.

  8. There is some evidence that protein aggregates can be passed from cell to cell, which may explain why the degeneration process can spread widely within the brain in Alzheimer's Disease.

  9. Key Words: intraneuronal inclusion bodies, neurofibrillary tangles, Lewy Bodies, beta-amyloid, Apoptosis







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