S100 Proteins in Alzheimer’s Disease

Abstract

S100 proteins are calcium-binding proteins that regulate several processes associated with Alzheimer’s disease (AD) but whose contribution and direct involvement in disease pathophysiology remains to be fully established. Due to neuroinflammation in AD patients, the levels of several S100 proteins are increased in the brain and some S100s play roles related to the processing of the amyloid precursor protein, regulation of amyloid beta peptide (Aβ) levels and Tau phosphorylation. S100 proteins are found associated with protein inclusions, either within plaques or as isolated S100-positive puncta, which suggests an active role in the formation of amyloid aggregates. Indeed, interactions between S100 proteins and aggregating Aβ indicate regulatory roles over the aggregation process, which may either delay or aggravate aggregation, depending on disease stage and relative S100 and Aβ levels. Additionally, S100s are also known to influence AD-related signaling pathways and levels of other cytokines. Recent evidence also suggests that metal-ligation by S100 proteins influences trace metal homeostasis in the brain, particularly of zinc, which is also a major deregulated process in AD. Altogether, this evidence strongly suggests a role of S100 proteins as key players in several AD-linked physiopathological processes, which we discuss in this review.

Friend or Foe: S100 Proteins in Cancer

“…Evaluated levels of several S100 proteins could also be observed in the brain of Alzheimer's patients. These S100 family members, namely S100A1, S100A6, S100A7, S100A8, S100A9, S100A12, and S100B, seem to be involved in the progression of Alzheimer's disease (AD), including the formation of amyloid aggregates, and could thereby be promising regarding new therapeutic approaches [66]. S100A1 seems to be an essential factor concerning cardiological diseases since it is involved in the contractile performance of cardiomyocytes [36,37].…”

Genome-wide identification of novel long non-coding RNAs and their possible roles in hypoxic zebrafish brain

“…Importantly, human brains showed a similar pattern of expression [53–55]. S100B acts as a pro-inflammatory cytokine, and several studies reported high levels of S100B in AD patients [56] and mouse models of AD [56]. Similarly, s100b expression in the zebrafish brain region was elevated.…”

Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers

“…Recently, the S100 family of proteins have been investigated for their role in AD, based on their ability to influence the Aβ aggregation pathway and its cellular receptors. While evidence shows that their function depends on the stage of pathology and related levels of Aβ and S100 proteins, it is possible that the S100 family could function as molecular chaperones to suppress oligomer toxicity through several mechanisms [ 169 , 170 ]. Development of chaperone-targeted therapeutics is limited by their stability, oral bioavailability, and blood–brain barrier permeability.…”