The Parkinson disease (PD) is a degenerative disorder of the central nervous system.
The motor symptoms of PD result from the loss of dopaminergic neurons in the
substantia nigra, which causes an insufficient formation and activity of
dopamine. The histopathologic correlate of the cell death are so called Lewy
bodies in neurons. Lewy bodies are inclusions of a protein called alpha-synuclein
in certain neurons within the brain stem and the basal ganglia. Alpha-synuclein
might be a promising future target.|
PD is, with a prevalence of 0.3% of the population in industrialized countries,
the second most common neurodegenerative disorder after Alzheimer's disease.
Mostly affected are the elderly, with a prevalence of 1% in the population over
60 years and 4% in those over 80 years. PD is idiopathic, although some genes
have been identified, which have a direct relation to some cases of PD.
Associated risk factors are certain pesticides and a reduced risk in tobacco
The typical symptoms are slowness of movement (bradykinesia) plus either
rigidity, resting tremor, or postural instability.|
For the medical treatment of PD there are a lot of therapeutics available,
which can reduce the symptoms. The most effective drug in reducing PD symptoms
is levodopa (L-dopa), which is a prodrug of dopamine and is usually administered
in combination with a dopa decarboxylase inhibitor (carbidopa, benserazide),
or a COMT inhibitor (entacapone, tolcapone, nitecapone) to ensure that L-dopa
is only converted to dopamine after crossing the blood brain barrier and not in
the periphery. L-dopa significantly increases the life expectancy of Parkinson's
patients, due to the reduction of disease-related complications. Unfortunately,
L-dopa has a bunch of side effects, for example dyskinesias.|
Other anti-parkinsonians are glutamate receptor (NMDA) antagonists,
anticholinergics, dopamine agonists and monoamino oxidase inhibitors (MAOI).
All of them have shown efficacy both in monotherapy and in combination with
L-Dopa. The L-Dopa sparing effect of a combination therapy delays the side effects,
particularly dyskinesias. Further promising targets are dopa transporters, and
tyrosine hydroxylases (dopa generation). Considering the apoptosis of dopaminergic
cells and it is important role in PD, anti-apoptotic therapy may be of interest,
but is not considered in here.|