Contemporary views on the pathogenesis of Parkinson’s disease

Abstract

Parkinson’s disease is e neurodegenerative disorder with unclear etiology, related to some genetic and environmental factors. It is not clear how the combination of these factors may cause neurodegeneration. Histologically Lewy bodies and neuritis are found in the degenerating neurons. They are composed mainly by protein aggregates, named α-synuclein. It is not known why the structure of α-synuclein is changed to the pathological β-spiral that aggregates and forms toxic oligomers, which cause degeneration of neurons. Recently the theory of prion spread of α-synuclein from the infected to healthy neurons is actual. The primary pathological changes during the preclinical phase of Parkinson’s disease appear in the olfactory system and gastrointestinal tract, where is probably the primary contact with the etiological agent. Lewy bodies are widespread and involve not only the dopaminergic neurons in substantia nigra, but many nondopaminergic neurons also. Degeneration is found in the cholinergic neurons of nucleus basalis Meynert, tegmentum of the midbrain, serotoninergic neurons of raphe nuclei, noradrenergic neurons of locus coeruleus and the pyramidal neurons in the pre-supplementary motor area of the cerebral cortex, connected with the cortico-cortical connections.
The early diagnosis of Parkinson’s disease is important in order to prevent the dissemination of the pathological protein and the neuronal degeneration. It is possible to find α-synuclein protein by endoscopic biopsy of the stomach mucosa and colonoscopy with biopsy. α-synuclein protein finding by cutaneous biopsy from regions with good autonomic innervation may be also an early marker of Parkinson’s disease.
A lot of drugs that may possibly slowdown the course of the disease are currently under examination. The most promising drugs target α-synuclein protein, the mechanisms of its distribution, and the systems of degradation or neutralization of the toxic protein.