2 5 7I n t h i s i s s u e . . .Parkinson’s disease
(PD) is a model neurodegenerative dis-order whose pathophysiology
was discovered years ago,and a rational treatment
was developed based on theknown neurotransmitter defect.
It set an early model forthe scientific understanding
of a single neurotransmitterillness, whose symptoms
improve with replacement of thattransmitter. Yet, identification
of the etiology (or etiologies)has lagged far behind, as
has the identification of an effec-tive prophylaxis. This
gap in understanding has not beenfor lack of creative, focused
research in pertinent areas,much of which is included
in this issue. The early discovery of
dopamine cell vulnerability in PDlaunched decades of research
into the anatomy, physiolo-gy, and pharmacology of
dopamine neuronal systems in thebrain. There now exists
a sophisticated understanding ofmany aspects of dopamine
function in the mammalianbrain. Because dopamine
is involved in mediating motor,cognitive, and affective
brain behaviors more broadly thanjust in PD, the extensive
knowledge generated by a focuson PD is applicable to
many other brain diseases. It wouldbe correct to say that
PD research has greatly advanced thestudy of many other diseases
of the brain. Moreover, anoth-er reason PD is particularly
important among brain diseasesis that it was the first
disease to demonstrate the role ofbasal ganglia function
(and dopaminergic activity) in mod-ulating motor, cognitive,
and affective behaviors in humans.The foundation of our understanding
of the critical influ-ence of dopamine on brain
function and human behaviorwere creatively developed
in the laboratory of Garrett E.Alexander and his collaborators.
His
State of the art arti-cle in this volume (page
259) tells us not only the historyof discovery in the area
of PD research, but also weaves inreference to all aspects
of PD biology; it is a rich criticalreview. His pioneering
work explained the mechanismswhereby dopaminergic activity
in the basal ganglia exten-sively influences cortical
function.Next, because the first
critical observations underlying ourunderstanding of PD pathophysiology
were made onhuman postmortem material,
postmortem research in thisarea has always been active.
In the first
Basic researcharticle, Andreas Hartmann
(page 281) has exhaustivelysummarized the postmortem
literature, always of pivotalinterest because of its
role in originally defining the illness.Then, Thomas Gasser (page
295) describes how the genet-ics of PD has helped advance
a molecular understandingof its etiology with the
discovery of several monogeneticfamilies, where a single
gene influences disease expression.While the disease overall
is not explained by a single geneor probably even a single
etiology, the few gene productsidentified in these families
have served to identify criticalmolecular processes influential
in the illness. The role thatstem cell research
could play in a disease like this
isdescribed in detail by
Lars M. Björklund (page 303), one ofthe pioneers in the field.
Therapeutic attempts in their veryearly stages of development
are described. Given the known molecular
target of PD, human brainimaging can be involved
in diagnosis, treatment, and eval-uation of course. In his
Poster article, Robert B. Innis(page 312) shows us this
molecular target and its currentimaging representations.In the
Pharmacological aspects article, Amos D. Korczyn(page 315) describes the
treatments for PD. Given the pre-cise molecular target
for PD, drug discovery has been pro-ductive over the years
and the clinical pharmacology rich.Again PD has anticipated
problematic clinical treatmentissues for brain diseases,
including optimal illness stage fortreatment onset, establishing
drug doses, and dealingwith drug-induced side
effects. Treatments for PD aresymptomatic; however,
prophylactic strategies are beingvigorously sought.Finally, in the area of
Clinical research, Karen E. Ander-son (page 323) describes
research in the clinically difficultareas of behavioral disturbances;
cognition and affectivechange in persons with
PD have their own unique expres-sions and treatment conditions.
Ian McKeith (page 333)then discusses the dementia
of Lewy body disease andcompares these syndromes
with the dementia of PD. We hope that this issue
is both scientifically interestingand clinically useful.
PD represents an illness where onediscovery generates a
world of new areas for research andan array of observations
important for treatment. PD hasled to advances in brain
research and has benefited fromadvances in other fields.
It is a model illness in its ability torepresent the steps that
can be taken to advance scientif-ic understanding in a
clinical disease.Carol A. Tamminga, MD
Alert