The long journey to the discovery of PARK2
The 50th Anniversary of Japanese Society of Neuropathology
Version of Record online: 27 JUL 2010
© 2010 Japanese Society of Neuropathology
Volume 30, Issue 5, pages 495–500, October 2010
How to Cite
Yamamura, Y. (2010), The long journey to the discovery of PARK2. Neuropathology, 30: 495–500. doi: 10.1111/j.1440-1789.2010.01144.x
- Issue online: 27 JUL 2010
- Version of Record online: 27 JUL 2010
- Received 9 April 2010; revised 28 April 2010 and accepted 29 April 2010; published online 27 July 2010.
- autosomal recessive inheritance;
- early-onset parkinsonism;
- Parkinson's disease;
- substantia nigra
Research into familial Parkinson's disease (PD) remained at a virtual standstill in Europe and the US for several decades until a re-challenge by Japanese neurologists regarding an autosomal recessive form of PD. In 1965, our research group at Nagoya University examined familial cases of early-onset parkinsonism characterized by autosomal recessive inheritance, diurnal fluctuation of symptoms (alleviation after sleep), foot dystonia, good response to medication, and benign course without dementia. An inborn error of metabolism in some dopamine-related pathway was suspected. The clinical study of four families with the disease, named as “early-onset parkinsonism with diurnal fluctuation (EPDF)”, was published in Neurology in 1973. The pathological study of a case in 1993 revealed neuronal loss without Lewy bodies in the substantia nigra. Based on these clinical and pathological evidences, EPDF was defined as a distinct disease entity. Screening for the EPDF gene was started in 1994 in collaboration with Juntendo University. With the discovery of parkin gene in 1998, EPDF was designated as PARK2. Of our 16 families examined for gene analysis, 15 proved to be PARK2, and the remaining one, PARK6.