Sporadic Parkinson's disease (sPD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic neurons in the substantia nigra. Although the pathogenesis of the disease remains undetermined, phosphorylation of ␣-synuclein and its oligomer formation seem to play a key role. However, the protein kinase(s) involved in the phosphorylation in the pathogenesis of sPD has not been identified. Here, we found that G-protein-coupled receptor kinase 5 (GRK5) accumulated in Lewy bodies and colocalized with ␣-synuclein in the pathological structures of the brains of sPD patients. In cotransfected cells, GRK5 phosphorylated Ser-129 of ␣-synuclein at the plasma membrane and induced translocation of phosphorylated ␣-synuclein to the perikaryal area. GRK5-catalyzed phosphorylation also promoted the formation of soluble oligomers and aggregates of ␣-synuclein. Genetic association study revealed haplotypic association of the GRK5 gene with susceptibility to sPD. The haplotype contained two functional single-nucleotide polymorphisms, m22.1 and m24, in introns of the GRK5 gene, which bound to YY1 (Yin Yang-1) and CREB-1 (cAMP response element-binding protein 1), respectively, and increased transcriptional activity of the reporter gene. The results suggest that phosphorylation of ␣-synuclein by GRK5 plays a crucial role in the pathogenesis of sPD.

Two cases of massive cerebral infarct in the territory of the middle cerebral artery on one side of the brain are presented, in which many (Patient 1) or several (Patient 2) neurofibrillary tangle-bearing neurons were observed in the nucleus basalis of Meynert (nbM), ipsilateral to the infarcts. Tangles were absent or rare in the opposite nbM or in other areas of the brain. Considering the widespread projection of nbM axons to the ipsilateral cerebral cortex, this suggests that formation of neurofibrillary tangles can occur as a retrograde reaction in nbM neurons secondary to massive, old cerebral infarction.

A male preponderance of Parkinson’s disease (PD) has been reported in European countries and the USA. To verify this issue in Japanese patients with PD, we examined the age- and gender-specific prevalence of PD in Yamagata Prefecture (population 1,244,040), Japan. The prevalence of PD was 61.3/100,000 men and 91.0/100,000 women, showing that women were significantly more affected by PD than men (p < 0.001). Contrary to the findings in Europe and the USA, the results indicate a female preponderance of PD among the Japanese population.

Tracheopathia osteochondroplastica (TO) is an unusual condition characterized by cartilaginous or bony submucosal nodules in the tracheobronchial tree. Bone morphogenetic protein-2 (BMP-2) and transforming growth factor beta-1 (TGF-beta 1) are potent inducers for new bone formation. We studied the precise localization of BMP-2 and TGF-beta 1 in two autopsied cases of TO, using immunohistochemical methods. Positive BMP-2 immunoreactivity was detected in numerous mesenchymal cells and chondroblasts lining the nodules in the tracheal submucosa. BMP-2 was not found in mature lamellar bony nodules. TGF-beta 1 was not seen in mesenchymal cells, though it did appear in chondrocytes and osteocytes in the nodules. These results suggest that BMP-2 plays an important role in nodule formation and acts synergistically with TGF-beta 1 to promote the nodules inductive cascade in the tracheal submucosa.

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