The Role of Osteopontin in Amyotrophic Lateral Sclerosis: A Systematic Review

Context: Osteopontin (OPN) is a matrix phosphoprotein expressed by a variety of tissues and cells, including the immune system and the nervous system. Previous studies have shown that OPN may have a role in neurodegenerative diseases, including multiple sclerosis, Parkinson's disease, and Alzheimer's disease. Objectives: The present study aimed to systematically review studies investigating the role of OPN in amyotrophic lateral sclerosis (ALS) patients or the disease animal model. Evidence Acquisition: We searched the Cochrane Library, PubMed, Web of Science, and Scopus to find relevant articles published up to January 20, 2019. Both human and animal model studies of ALS were considered. Results: A total of nine articles (four human studies and five animal model studies) were included. Two of the human studies reported that the CSF levels of OPN were higher among ALS patients compared to controls. The other two human studies found that OPN levels in cortical neurons did not differ significantly between ALS cases and the non-neurological control group. One of the studies found that the expression level of OPN in astrocytes was similar between ALS patients and the control group, but the level of microglial OPN significantly increased in ALS cases. Four of the animal model studies reported that the expression of OPN mRNA in spinal cord microglia significantly increased during the disease progression. The remaining animal model study found that OPN was selectively expressed by fast fatigue-resistant and slow motor neurons (MNs), which are resistant to ALS, and that the OPN expression was low among fast-fatigable MNs. Conclusions: Prompt microglial activation is a hallmark pathology of ALS, and OPN is among the most widely expressed proteins by these activated glial cells. Therefore, OPN might have a role in ALS pathogenesis. The existing evidence is not sufficient to justify whether OPN has a neurotoxic or neuroprotective role in ALS. We encourage researchers to investigate the role of OPN in ALS pathogenesis more extensively.