Osteonectin Protein May Play Role in Parkinson’s, Other Neurodegenerative Diseases

A protein called osteonectin may be implicated in Parkinson’s and other neurodegenerative diseases, according to a computer-based analysis.

The study, “In silico method for identification of novel copper and iron metabolism proteins in various neurodegenerative disorders,” was published  in the journal NeuroToxicology.

Excessive production of copper and iron leads to oxidative stress, which particularly affects the central nervous system. Oxidative stress is an imbalance between the production of free radicals and the ability of cells to detoxify them. These free radicals or reactive oxygen species are harmful to the cells and are associated with a number of diseases, including Parkinson’s.

Altered copper and iron levels have been associated with neurodegenerative diseases such as Parkinson’s, Alzheimer’s and Huntington’s. Alpha-synuclein, the main component of Lewy bodies in Parkinson’s is itself a copper-binding protein, whose aggregation is promoted by both copper and iron.

However, the exact role of copper and iron toxicity in nerve cell death and disease progression remains unclear. A further challenge is the extensive network of interactions between metals and proteins, which changes with age, disease and treatment.

In this study, researchers used an approach called network biology to assess all proteins implicated in copper and iron metabolism with the goal of determining their interactions in different neurodegenerative diseases.

In total, the in silico (computer-based) assessment initially included 204 proteins implicated in copper, and 441 in iron metabolism. But these numbers increased to 1,175 and 2,529, respectively, after obtaining the protein-protein interaction networks. Also, there were 1,350 interactions related to copper and 7,233 related to iron proteins.

After searching for connections that could be part of a protein complex or pathway and merging the interaction networks of copper and iron to find common proteins, the investigators assessed their association with different diseases.

The results revealed that osteonectin and the clotting proteins factor V and VII could be involved in different neurodegenerative diseases. Specifically, osteonectin, a protein found at increased levels in cancer and with a protective role against oxidative stress, may be implicated in Parkinson’s, Alzheimer’s, and Huntington’s diseases, and neurodegeneration with brain iron accumulation disorders.

Expression of the SPARC gene, which codes for osteonectin, is found in different brain regions and has been associated with protection from neuroinflammation.

In turn, factor V may be involved in Brunner syndrome, obsessive-compulsive disorder, febrile seizures and schizophrenia, and factor VII in L1 syndrome and congenital hydrocephalus.

The literature on the links between clotting proteins and neurodegenerative diseases is scarce, researchers noted, although variants in F5, the gene coding for factor V, have been associated with Alzheimer’s.

“In conclusion, the present study shows the first evidence in silico that SPARC/osteonectin, Coagulation factor V and VII proteins may have plausible role in the pathogenesis of various neurodegenerative diseases,” researchers wrote.