臨床神経学

<シンポジウム26―1>変性疾患のシード・凝集・神経回路網伝搬仮説の検証

変性疾患 蛋白伝搬仮説の検証

村山 繁雄

東京都健康長寿医療センター高齢者ブレインバンク〔〒173―0015 東京都板橋区栄町35―2〕

Braak proposed propagation staging paradigm of Lewy-related alpha-synucleinopathy, which starts from medulla oblongata and extends rostrally to neocortex. Since this propagation shares that of bovine spongiformic encephalopathy, alpha-synuclein-prionopathy hypothesis was presented and augumented by pathological reports of Lewy body pathology in fetal tansplants of midbrain to patients with Parkinson disease (PD). The prionopathy hypothesis expanded to include tau and TDP-43, is now receiving considerable attention world wide. Laterality of clinical symptoms can be explained with this hypothesis in PD, amyotrophic lateral sclerosis-TDP43, frontotemoral lobar degeneration-semantic dementia-TDP43 and tauopathy including corticobasal degeneration and argyrophilic grain dementia. Major cons of prionopathy hypothesis is how to explain cell to cell transmission of intracellular amyloid-like proteins. Several clinical and experimental data are now accumulated to answer this question. The difference in speed of spread between prion disease and neurodegenerative disease could be explained by aggregation size of abnormal proteins. The hypothesis could also explain glinoneuronal interaction, which is receiving another hot topic of neurodeneration. We propose that seed, aggregation propagation of abnormal protein should form one factor of clinical progression of neurodegenerative diseases and can be a therapeutic targets in future research.
Full Text of this Article in Japanese PDF (477K)

(臨床神経, 51:1097−1099, 2011)
key words:タウ,αシヌクレイン,TDP-43,プリオン,アミロイドβ蛋白

(受付日:2011年5月20日)