by Rolf Hassler in 1938. The underlying biochemical changes in the brain were identified in the 1950s, due largely to the work of Arvid Carlsson on the neurotransmitter dopamine and Oleh Hornykiewicz on its role on PD. Carlsson was eventually awarded a Nobel Prize for this work. Alice Lazzarini et al pinpointed a genetic component to PD in 1994. Years earlier, the neurology clinic at Robert Wood Johnson Medical School (RWJMS) had located a family of Italian origin that encompassed at least five generations of more than 400 individuals and at least 60 members with PD, and traced their ancestors to the small village of Contursi, Italy. In 1995, the RWJMS team joined with the National Center for Human Genome Research at the National Institutes of Health to take advantage of the laboratory resources available from the NIH in an effort to locate the gene causing PD in the Contursi family. The team reported the first Parkinson disease-causing mutation (PARK1) in the brain protein, alpha-synuclein. Within days of the publication of the PARK1 findings, alpha-synuclein was discovered to be the major component of Lewy bodies within brain cells of PD patients; according to the UMDNJ magazine, "This discovery changed the direction of research into PD by providing scientists with an entirely new protein whose manufacture, function or breakdown could be the key to the disease." Synuclein proteins being the main component of Lewy bodies was discovered in 1997 by Spillantini, Trojanowski, Goedert and others. Mutations in the parkin gene in autosomal recessive juvenile parkinsonism were discovered in 1998 and finally, between 2002-2005, DJ-1 gene mutations, PINK1 gene mutations and the most common mutations in the LRRK2 gene were identified in Japanese and European families. The pathological staging in Parkinson's disease was described by Heiko Braak in 2003. History of treatments The positive albeit modest effects on tremor of anticholinergic alkaloids obtained from the plant of the belladona were described during 19th century by Charcot, Erb and others. Modern surgery for tremor, consisting of the lesioning of some of the basal ganglia structures was first tried in 1939 and was improved over the following 20 years. Before this date surgery consisted in lesioning the corticospinal pathway with paralysis instead of tremor as result. Anticholinergics and surgery were the only treaments until the arrival of levodopa, which reduced their use dramatically. Levodopa was first synthesized in 1911 by Casimir Funk, but it received little attention until the mid 20th century. It entered clinical practice in 1967, and the first large study reporting improvements in people with Parkinson's disease resulting from treatment with levodopa was published in 1968. Levodopa brought about a revolution in the management of PD. By the late 1980s deep brain stimulation introduced by Alim-Louis Benabid and colleagues at Grenoble, France, emerged as a possible treatment and it was approved for clinical use by the FDA in 1997. References Category:Parkinson's disease