Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
Volume 93 , Issue 6
Showing 1-4 articles out of 4 articles from the selected issue
Review
  • Hitoshi OKAZAWA
    2017 Volume 93 Issue 6 Pages 361-377
    Published: June 09, 2017
    Released: June 12, 2017
    JOURNALS FREE ACCESS FULL-TEXT HTML

    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-Aβ 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.

  • Satoko ARAKAWA, Shinya HONDA, Hirofumi YAMAGUCHI, Shigeomi SHIMIZU
    2017 Volume 93 Issue 6 Pages 378-385
    Published: June 09, 2017
    Released: June 12, 2017
    JOURNALS FREE ACCESS FULL-TEXT HTML

    ATG5 and ATG7 are considered to be essential molecules for the induction of autophagy. However, we found that cells lacking ATG5 or ATG7 can still form autophagosomes/autolysosomes and perform autophagic protein degradation when subjected to certain types of stress. Although the lipidation of LC3 is accepted as a good indicator of autophagy, this did not occur during ATG5/ATG7-independent alternative autophagy. Unlike conventional autophagy, autophagosomes appeared to be generated in a Rab9-dependent manner by the fusion of the phagophores with vesicles derived from the trans-Golgi and late endosomes. Therefore, mammalian autophagy can occur via at least two different pathways; the ATG5/ATG7-dependent conventional pathway and an ATG5/ATG7-independent alternative pathway.

  • Jun TAKOUDA, Sayako KATADA, Kinichi NAKASHIMA
    2017 Volume 93 Issue 6 Pages 386-398
    Published: June 09, 2017
    Released: June 12, 2017
    JOURNALS FREE ACCESS FULL-TEXT HTML

    In the developing brain, the three major cell types, i.e., neurons, astrocytes and oligodendrocytes, are generated from common multipotent neural stem cells (NSCs). In particular, astrocytes eventually occupy a great fraction of the brain and play pivotal roles in the brain development and functions. However, NSCs cannot produce the three major cell types simultaneously from the beginning; e.g., it is known that neurogenesis precedes astrogenesis during brain development. How is this fate switching achieved? Many studies have revealed that extracellular cues and intracellular programs are involved in the transition of NSC fate specification. The former include growth factor- and cytokine-signaling, and the latter involve epigenetic machinery, including DNA methylation, histone modifications, and non-coding RNAs. Accumulating evidence has identified a complex array of epigenetic modifications that control the timing of astrocytic differentiation of NSCs. In this review, we introduce recent progress in identifying the molecular mechanisms of astrogenesis underlying the tight regulation of neuronal-astrocytic fate switching of NSCs.

Original Article
feedback
Top