A gene for Parkinson disease
T. N. Chase
Experimental Therapeutics Branch, National Institute of Neurological, Disorders and Stroke, National Institues of Health, Bethesda, Md., USA.
Until recently, the possibility that genetic factors contributed
significantly to the pathogenesis of Parkinson disease (PD) was accorded
relatively short shift. Few patients with obviously familial PD are seen in
common practice, and families with parkinsonism often present with rather
atypical features. The discovery that the neurotoxin
N-methyltetrahydropyridine (MPTP) rapidly induces an illness similar to
sporadic PD added fuel to those arguing that environmental factors must be
largely responsible. But more recently, this view has begun to shift
because no generally plausible environmental factors emerged and data
favoring a genetic component began to mount. Now it is clear that the cause
of PD may on occasion be purely genetic and involve autosomal dominant as
well as various other inheritance patterns. Moreover, it has become
increasingly apparent that even in sporadic cases, the disease most likely
reflects some combination of genetic susceptibility and environmental
insult. In such instances, the genetic component presumably acts by
increasing the vulnerability of dopamine-containing neurons in the
nigrostriatal system to injury by 1 or more common, possibly by themselves
relatively innocuous, environmental factors. This view has now been
substantially reinforced and our ability to understand the pathogenesis of
PD dramatically advanced by the recent identification of a gene responsible
for PD in 4 unrelated families.
