Rinshō shinkeigaku = Clinical neurology
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Cardiac uptake of meta-iodobenzylguanidine (MIBG) is specifically reduced in Lewy body disease (LBD). To see pathological basis of the reduced cardiac uptake of MIBG in LBD, we immunohistichemically examined cardiac tissues from patients with LBD, related movement disorders and Alzheimer's disease (AD). In LBD, cardiac sympathetic denervation occurs, which accounts for the reduced cardiac uptake of MIBG. ⋯ We further investigate how a-synuclein aggregates are involved in degeneration of the cardiac sympathetic nerve in PD. Accumulation of alpha-synuclein aggregates in the distal axons of the cardiac sympathetic nervous system precedes that of neuronal somata or neurites in the paravertebral sympathetic ganglia and that it heralds centripetal degeneration of the cardiac sympathetic nerve in PD. This chronological and dynamic relationship between alpha-synuclein aggregates and degeneration of the cardiac sympathetic nervous system may represent the pathological mechanism underlying a common degenerative process in PD.
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Genetic and biological studies provide evidence that the production and deposition of amyloid-beta peptides (Abeta) contribute to the etiology of Alzheimer's disease. Thus, beta- and gamma-secretases, that are involved in the Abeta generation, are plausible molecular targets for Alzheimer's disease treatment. gamma-Secretase is an unusual aspartic protease that cleaves the scissile bond within the transmembrane domain. ⋯ Thus, understanding the molecular mechanism whereby gamma-secretase recognizes and cleaves its substrate is a critical issue for the development of compounds that specifically regulate Abeta-generating gamma-secretase activity. I will review our structural studies on the gamma-secretase complex, and envision the direction for developing effective and selective gamma-secretase inhibitors as therapeutics for AD.
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The blood-nerve barrier (BNB) is one of the functional barriers sheltering the nervous system from systemic blood. Although BNB is effective in controlling the endoneurial environment in normal condition, it may interfere the entrance of beneficial substances including various growth factors into the endoneurial space and inhibit the axonal regeneration in peripheral neuropathy. ⋯ We also obtained immortal endothelial and pericyte cell lines originating from human BNB. Analyses of physiological characteristics and protein profiles in these BNB-forming cells are underway in our laboratory.