The viral hypothesis in parkinsonism.
The most crucial unanswered question in Parkinson's disease is its fundamental cause. Since Carlsson's original suggestion that dopamine may be a transmitter in the central nervous system involved in the control of motor function and that it may be involved in the Parkinsonian syndrome (Carlsson, 1959), and the now-classic paper by Ehringer and Hornykiewicz (1960) which definitively showed the significant reduction of dopamine concentration in the neostriatum of cases of idiopathic Parkinson and postencephalitic parkinsonism, the vast amount of work on the subject has focused on the biochemical and pharmacologic correlates of this dopaminergic system failure involving particularly the nigrostriatal pathways. The concept of a specific neurotransmitter deficiency associated with a specific neurological syndrome potentially amenable to replacement therapy, has appropriately generated a considerable degree of clinical and research interest for over 20 years, but, with few exceptions, there has been hardly any focused or concerted research effort on looking at direct causal factors or primary initiating events in this disease process. As in Alzheimer's disease, another of the degenerative diseases of the brain of unknown origin with a specific biochemical substrate, any etiologic hypothesis for Parkinson's disease--whether a virus, an age-related immune system dysfunction, a genetic factor, a "trophic" substance, or a toxin--would have to explain the selective involvement of specific transmitter-defined neuronal pathways, the non-specificity of the brain lesions that define the disease, and the clinical involvement of a sizeable segment of the aging population. Of the several plausible hypotheses mentioned earlier, which are not necessarily mutually exclusive, we would like to critically consider the possibility of a viral cause.
D000544:Alzheimer Disease / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis*; D001323:Autoantibodies / Q000032:analysis; D001921:Brain / Q000276:immunology; D003599:Cytoskeleton / Q000276:immunology; D003704:Dementia / Q000276:immunology; D004298:Dopamine / Q000378:metabolism; D006561:Herpes Simplex / Q000276:immunology; D006801:Humans; D010300:Parkinson Disease / Q000276:immunology*; D010301:Parkinson Disease, Postencephalitic / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D000914:Antibodies, Viral; D001323:Autoantibodies; D004298:Dopamine