中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (11): 1776-1779.doi: 10.4103/1673-5374.219031

• 综述:退行性病与再生 • 上一篇    下一篇

取出垃圾:组织蛋白酶D和神经退化中的钙调神经磷酸酶

  

  • 收稿日期:2017-11-14 出版日期:2017-11-15 发布日期:2017-11-15

Taking out the garbage: cathepsin D and calcineurin in neurodegeneration

Andreas Aufschnaiter1, Verena Kohler1, Sabrina Büttner1, 2   

  1. 1 Institute of Molecular Biosciences, University of Graz, Humboldtstraße 50, 8010 Graz, Austria
    2 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Svante Arrheniusväg 20C, 106 91 Stockholm, Sweden
  • Received:2017-11-14 Online:2017-11-15 Published:2017-11-15
  • Contact: Sabrina Büttner,sabrina.buettner@su.se.
  • Supported by:

    This work was supported by the Austrian Science Fund FWF (No. P27183-B24), the Swedish Research Council Vetenskapsrådet (No.2015-05468), Åke Wiberg Stiftelse (No. M16-0130), Carl Trygger Stiftlese (No. CTS16:85), and Goljes Stiftelse (No. LA2016-0123).

摘要:

orcid:0000-0002-2786-8542(Sabrina Büttner)

Abstract:

Cellular homeostasis requires a tightly controlled balance between protein synthesis, folding and degradation. Especially long-lived, post-mitotic cells such as neurons depend on an efficient proteostasis system to maintain cellular health over decades. Thus, a functional decline of processes contributing to protein degradation such as autophagy and general lysosomal proteolytic capacity is connected to several age-associated neurodegenerative disorders, including Parkinson’s, Alzheimer’s and Huntington’s diseases. These so called proteinopathies are characterized by the accumulation and misfolding of distinct proteins, subsequently driving cellular demise. We recently linked efficient lysosomal protein breakdown via the protease cathepsin D to the Ca2+/calmodulin-activated phosphatase calcineurin. In a yeast model for Parkinson’s disease, functional calcineurin was required for proper trafficking of cathepsin D to the lysosome and for recycling of its endosomal sorting receptor to allow further rounds of shuttling. Here, we discuss these findings in relation to present knowledge about the involvement of cathepsin D in proteinopathies in general and a possible connection between this protease, calcineurin signalling and endosomal sorting in particular. As dysregulation of Ca2+ homeostasis as well as lysosomal impairment is connected to a plethora of neurodegenerative disorders, this novel interplay might very well impact pathologies beyond Parkinson’s disease.

Key words: neurodegeneration, Parkinson’s disease, α-synuclein, cathepsin D, calcineurin, retromer, yeast, lysosome, endosomal sorting