Why is the substantia nigra specifically affected in Parkinson's?

The underlying cause of Parkinson’s is the loss of dopamine producing nerve cells in the substantia nigra, a structure of the brain. This raises the question, why aren’t other cells of the body also affected?

We have 30,000 genes (which are made of DNA) in each cell of our body; we may be carrying mutations in one or more of these genes that make us susceptible to a disease. If we compare a skin cell with a nerve cell, both types of cell have the full complement of genes inside them. What is different is that the skin cell has activated a distinct subset of genes (these genes are said to be “expressed”) while the nerve cell expresses a different subset of genes. The action of these different sets of genes imparts the distinctive characteristics of a skin cell and nerve cell. Nerve cell genes are present in skin cells but they have no effect because they are switched off (i.e. they are not expressed). It is the same with skin cell genes in nerve cells. Incidentally, the generation of cloned animals from adult cells is made possible because cells retain all their genes; part of the cloning process is resetting all gene expression back to zero to allow all cell types to develop in the clone. If skin cells had only skin cell genes then cloning a skin cell would end up with a cloned animal made of only skin cells!

Back to the question! Nerve cells naturally express nerve cell genes. If a mutation is present in a skin cell gene (and it disrupts normal function of that gene) it will not affect nerve cells because the gene is switched off in these cells and has no influence; a faulty light bulb has no effect if it remains switched off. The mutation will, of course, affect skin cells. Therefore, the substantia nigra is affected in Parkinson’s disease because mutations are present in nerve cell genes specifically expressed in the substantia nigra.