From the origins of paralysis agitans to the development of its experimental model

Abstract

The importance of looking backwards regarding Parkinson disease (PD) lies in understanding its early description and classification to direct us towards its treatment. Documents from 4,000 years ago include clinical signs of the disease, in 1817 James Parkinson described it as a neurological disorder called “paralysis agitans”; Martin Charcot completed the syndrome description, identifying bradikinesia, different types of tremor, non-motor symptoms and the term “Parkinson disease” was employed. Brissaud proposed that damage in the substantia nigra was the underlying pathology of PD. From the elucidation of its pathophysiology and the development of experimental models mimicking some characteristics of the disease, it has been possible to establish some therapeutic strategies. Several models exist which show both advantages and disadvantages, like 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat and rotenone. MTPT was discovered by serendipity in intravenous drug users. Even though no model replicates the whole disease, due to its high reproducibility, the presence of both motor and non-motor symptoms as well as Lewy bodies, and mainly, because of its selectivity for damaging the substantia nigra, the use of MTPT in monkeys is considered the gold standard; thus, a fortunate finding becomes a valuable experimental tool.