Neurodegeneration in Alzheimer's and Parkinson's

By Dr Ananya Mandal, MD

Neurodegeneration involves loss of structure and function of the nerve cells in the brain. Two of the most common neurodegenerative diseases are Alzheimer's disease and Parkinson's disease. These disease conditions have different characteristics in terms of symptoms, signs and progression. However, they share a similar mechanism of pathology that involves the accumulation of abnormally folded proteins that leads to fibril formation and amyloidosis.

Neurodegeneration in Alzheimer's disease

Alzheimer's disease is characterized by a loss of neurons and synapses in the cerebral cortex and some major brain areas that lie below the cortex. This eventually leads to atrophy and degeneration of areas such as the temporal and parietal lobes, the frontal cortex and the cingulate gyrus.

Alzheimer's disease primarily arises from misfolding of the beta-amyloid and tau proteins. In healthy individuals, proteins are formed of long chains of amino acids that are folded in a particular 3D conformation.

In Alzheimer's disease, however, there is an abnormality of this folding that results in the aggregation of misfolded proteins that are deposited in various parts of the brain. These deposits are small peptides of are around 39-43 amino acids in length and are called beta-amyloid proteins.

The beta amyloid is a fragment of a larger protein called amyloid precursor protein (APP) that is usually involved in neuronal growth and repair after injury. In Alzheimer's disease, however, an unknown mechanism causes APP to be split up into smaller fragments that can give rise to the beta-amyloid fibrils.

Neurodegeneration in Parkinson's disease

The main cause of Parkinson's disease is death of the cells in the pars compacta of the substantia nigra, that secrete dopamine. The exact mechanism by which these cells are lost is not clear but one suggested theory is that there is an abnormal accumulation of a protein called alpha-synuclein bound to ubiquitin in nerve cells.

These accumulating proteins form spherical inclusions called Lewy bodies which are thought to exert harmful effects by disrupting the normal chemical signalling between cells in certain areas of the brain. This may result in dysfunction of the nerve cells that initiate the movement of muscles, for example.

Reviewed by Sally Robertson, BSc

Sources

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