Lysosome storage disorders on the brain: The autophagy lysosome pathway contributes to disease pathophysiology and may be utilized for therapeutic benefit



  • Lysosome storage disorders (LSDs) are defined by genetic mutations that either directly or indirectly compromise lysosome function, many of which exhibit documented CNS pathophysiology. As lysosome dysfunction is a principal contributing factor to the onset and progression of LSDs, it is not surprising to learn of several reports documenting inherent abnormalities in the autophagy-lysosome pathway (ALP), as the ALP requires itntact lysosome function for its proper clearance of substrates and homeostatic maintenance of energy balance. In addition, accumulating evidence suggests that alterations in ALP signaling contribute to the onset and progression of adult onset neurodegenerative disease. Thus the study of LSD mutations and their effects on the ALP has aided in our understanding of ALP-associated contributions to diseases such as Alzheimer’s and Parkinson’s. Herein we will review LSDs with known CNS pathophysiology and will discuss the often heterogeneous ALP abnormalities amongst these diseases. LSD-specific therapies will also be discussed and how the ALP may be a direct or indirect target of such therapies. Finally, the function of the ALP in LSDs will be discussed relative to its putative role in adult onset neurodegenerative disease.
  • Authors

    Digital Object Identifier (doi)

    International Standard Book Number (isbn) 13

  • 9789814350440
  • Start Page

  • 331
  • End Page

  • 354