Protective mechanisms by cystatin C in neurodegenerative diseases

Front Biosci (Schol Ed). 2011 Jan 1;3:541-54. doi: 10.2741/s170.


Neurodegeneration occurs in acute pathological conditions such as stroke, ischemia, and head trauma and in chronic disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. While the cause of neuronal death is different and not always known in these varied conditions, hindrance of cell death would be beneficial in the prevention of, slowing of, or halting disease progression. Enhanced cystatin C (CysC) expression in these conditions caused a debate as to whether CysC up-regulation facilitates neurodegeneration or it is an endogenous neuroprotective attempt to prevent the progression of the pathology. However, recent in vitro and in vivo data have demonstrated that CysC plays protective roles via pathways that are dependent on inhibition of cysteine proteases, such as cathepsin B, or by induction of autophagy, induction of proliferation, and inhibition of amyloid-beta aggregation. Here we review the data demonstrating the protective roles of CysC under conditions of neuronal challenge and the protective pathways induced under various conditions. These data suggest that CysC is a therapeutic candidate that can potentially prevent brain damage and neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid / antagonists & inhibitors
  • Animals
  • Autophagy / drug effects
  • Autophagy / physiology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cystatin C / metabolism
  • Cystatin C / therapeutic use*
  • Cysteine Proteinase Inhibitors / metabolism
  • Cysteine Proteinase Inhibitors / therapeutic use*
  • Cytoprotection*
  • Gene Expression Regulation / physiology
  • Humans
  • Mice
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / prevention & control*
  • Neurogenesis / drug effects*
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / therapeutic use*


  • Amyloid
  • Cystatin C
  • Cysteine Proteinase Inhibitors
  • Neuroprotective Agents