From Drugs of Abuse to Parkinsonism: The MPTP Mouse Model of Parkinson’s Disease - Drugs of Abuse: Neurological Reviews and Protocols - page 102

Fig. 1. Cumulative number of publications on MPTP studies since 1983. Source:
Medlines.

within the substantia nigra are lost at a relatively accelerated rate compared to
the normal aging process (5 , 6) . In human PD, clinical symptoms do not fully
develop until at least 70-80% of the striatal nerve terminals and 50-60% of the
substantia nigra pars compacta cells are permanently lost (7-11) . As a result of
neuronal cell death and terminal loss, the neurochemical synthesis and release
of the key transmitter, dopamine (DA), in the basal ganglia are dysfunctional
and insuffi cient. Current drug therapy with 3,4-dihydroxy- L -phenylalanine
( L -DOPA) or DA agonists only corrects the symptoms temporarily, but does
not alter the course of the disease or protect neurons from degeneration due
to unknown causes.
Pathologically, PD is characteristically accompanied by widespread forma-
tion of Lewy bodies and dystrophic neurites detected in the degenerated
nigrostriatal dopaminergic and other cortical/subcortical neurons postmortem
(12 , 13) . Lewy bodies found in the substantia nigra and locus ceruleus of PD
are typically described as concentric, intracytoplasmic inclusions consisting
of a dense granular core and surrounded by a halo of radiating fi laments (13) .
The Lewy bodies exhibit abnormally phosphorylated neurofi laments with
an accumulation of proteins (such as ubiquitin and -synuclein) and lipids

(14-18) . The major clinical and neuropathological features of human PD are
summarized in Table 1 .

3. Research Models of PD
To establish a valid experimental model that closely resembles PD by
keeping the cardinal symptomatology of human PD in mind (Table 1) , the