Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases

被引:9
作者
Okazawa, Hitoshi [1 ,2 ]
机构
[1] Tokyo Med & Dent Univ, Dept Neuropathol, Med Res Inst, Tokyo, Japan
[2] Tokyo Med & Dent Univ, Ctr Brain Integrat Res, Tokyo, Japan
来源
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES | 2017年 / 93卷 / 06期
基金
日本学术振兴会; 日本科学技术振兴机构;
关键词
Ultra-Early Phase pathology; amyloid hypothesis; intracellular amyloid; Alzheimer's disease; neurodegeneration; Huntington's disease; POLYGLUTAMINE TRACT-BINDING; AMYLOID PRECURSOR PROTEIN; LINKED MENTAL-RETARDATION; INTRACELLULAR ACCUMULATION; PQBP1; GENE; MUTANT HUNTINGTIN; CELL-DEATH; BETA; MUTATIONS; DOMAIN;
D O I
10.2183/pjab.93.022
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-A beta antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.
引用
收藏
页码:361 / 377
页数:17
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