• Introduction

• Epidemiology

• Symptoms

• Pathology

• Aetiology

• Overview

• Pharmacological

• Other methods

Aetiology

Although the causes of PD are not yet fully understood, a number of risk factors have been identified. The first is, simply, age. As mentioned previously, the majority of cases are late-onset. However, it is important to note that the disease symptoms are not part of the normal aging process. The second risk factor is a family history of the disease. A number of such families have been identified and in many cases so have the associated mutations.

Other risk factors include head injury and exposure to a variety of chemicals, some of which are known to cause forms of secondary Parkinsonism. These toxins include managanese (linked with a Parkinsonian disorder called "Manganese Madness"), carbon disulphide and MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; a contaminant of the active component of a particular "designer drug").

Proposed mechanisms of neurodegeneration include "oxidative stress" and protein dysfunction. Reactive molecules called free radicals — byproducts of a number of biochemical reactions — can react with cellular constituents such as proteins, causing damage. There are cellular mechanisms to clear up these molecules and repair the damage, but these can prove inadequate (a state known as oxidative stress). This damage then builds up until the cell can no longer function. Nigral cells are particularly susceptible to oxidative stress because of their high levels of iron. Iron is a strong stimulator of free radical formation.

Abnormal protein aggregation (especially in the form of Lewy bodies) is diagnostic for PD. In addition, some cases of the disease have been associated with specific mutations. It seems likely, therefore, that protein dysfunction — whether loss of normal function or toxic gain of function — plays an important role in the disease process. Many of the proteins believed to be dysfunctional are associated with the ubiquitin proteasome pathway. This is responsible for removing damed or misfolded proteins, so any disruption of this pathway could result in the accumulation of even more abnormal protein.