A LOSS-OF-FUNCTION MECHANISM OF NIGRAL NEURON DEATH WITHOUT LEWY BODYFORMATION - AUTOSOMAL RECESSIVE JUVENILE PARKINSONISM (AR-JP)

We present a genetic model of selective nigral neuron death without Le wy body formation - autosomal recessive juvenile parkinsonism (AR-JP). Mapping of AR-JP gene to a single recessive locus on chromosome 6q25. 2-27 is a strong indication of the idea that a loss-of-function mutati on of a single gene is sufficient to cause selective nigral neuron dea th. The absence of Lewy body formation in AR-JP is important, because most cases of neuron death caused by loss-of-function mechanism are no t accompanied by inclusion body. Our findings clearly indicate that ni gral cells are critically dependent for their survival on the function of AR-JP protein. This raises an important question of whether or not AR-JP protein contributes to the downstream pathway of cell death in Parkinson's disease.