A loss-of-function mechanism of nigral neuron death without Lewy body formation: autosomal recessive juvenile parkinsonism (AR-JP).
We present a genetic model of selective nigral neuron death without Lewy 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 mutation of a single gene is sufficient to cause selective nigral neuron death. The absence of Lewy body formation in AR-JP is important, because most cases of neuron death caused by loss-of-function mechanism are not accompanied by inclusion body. Our findings clearly indicate that nigral 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.
Matsumine
H
H
Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo, Japan. hmatumi@med.juntendo.ac.jp
D016923:Cell Death; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D017353:Gene Deletion; D005808:Genes, Recessive; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D008957:Models, Genetic; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology; D013378:Substantia Nigra / Q000473:pathology*