S100A6 and Its Brain Ligands in Neurodegenerative Disorders

Abstract

The S100A6 protein is present in different mammalian cells and tissues including the brain. It binds Ca²⁺ and Zn²⁺ and interacts with many target proteins/ligands. The best characterized ligands of S100A6, expressed at high level in the brain, include CacyBP/SIP and Sgt1. Research concerning the functional role of S100A6 and these two ligands indicates that they are involved in various signaling pathways that regulate cell proliferation, differentiation, cytoskeletal organization, and others. In this review, we focused on the expression/localization of these proteins in the brain and on their possible role in neurodegenerative diseases. Published results demonstrate that S100A6, CacyBP/SIP, and Sgt1 are expressed in various brain structures and in the spinal cord and can be found in different cell types including neurons and astrocytes. When it comes to their possible involvement in nervous system pathology, it is evident that their expression/level and/or subcellular localization is changed when compared to normal conditions. Among diseases in which such changes have been observed are Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), epileptogenesis, Parkinson's disease (PD), Huntington's disease (HD), and others.

Keywords: CacyBP/SIP; Lewy bodies; S100A6; Sgt1; neurodegeneration; neurofibrillary tangles; β amyloid plaques.

Figure 1

Structure of S100A6 dimer loaded with 4 Ca²⁺ (Protein Data Bank id:1K96) [3]. Each color, blue and red, represents one monomer; yellow balls represent Ca²⁺.