Title:Does Ceruloplasmin Defend Against Neurodegenerative Diseases?
Volume: 17
Issue: 6
Author(s): Bo Wang and Xiao-Ping Wang*
Affiliation:
- Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080,China
Keywords:
Ceruloplasmin, iron, copper, oxidative stress, free radicals, neurodegeneration, neurodegenerative diseases.
Abstract: Ceruloplasmin (CP) is the major copper transport protein in plasma, mainly produced by
the liver. Glycosylphosphatidylinositol-linked CP (GPI-CP) is the predominant form expressed in
astrocytes of the brain. A growing body of evidence has demonstrated that CP is an essential protein
in the body with multiple functions such as regulating the homeostasis of copper and iron ions,
ferroxidase activity, oxidizing organic amines, and preventing the formation of free radicals. In
addition, as an acute-phase protein, CP is induced during inflammation and infection. The fact that
patients with genetic disorder aceruloplasminemia do not suffer from tissue copper deficiency, but
rather from disruptions in iron metabolism shows essential roles of CP in iron metabolism rather
than copper. Furthermore, abnormal metabolism of metal ions and oxidative stress are found in
other neurodegenerative diseases, such as Wilson’s disease, Alzheimer’s disease and Parkinson’s
disease. Brain iron accumulation and decreased activity of CP have been shown to be associated
with neurodegeneration. We hypothesize that CP may play a protective role in neurodegenerative
diseases. However, whether iron accumulation is a cause or a result of neurodegeneration remains
unclear. Further research on molecular mechanisms is required before a consensus can be reached
regarding a neuroprotective role for CP in neurodegeneration. This review article summarizes
the main physiological functions of CP and the current knowledge of its role in neurodegenerative
diseases.