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.
Highlights
Reviewed by: Estelle Leclerc, North Dakota State University, United States Wieslawa Lesniak, Nencki Institute of Experimental Biology (PAS), Poland
Due to neuroinflammation in Alzheimer’s disease (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
In the amyloidogenic pathway, amyloid precursor protein (APP) is cleaved by β- and γ-secretase producing sAPPβ, C-terminal fragments and amyloid-β peptide (Aβ) peptides, which promote a range of detrimental effects in neurons and in the brain (Ling et al, 2003)
Summary
Evidence suggests that S100B may regulate plaque formation as the knockout of S100B in the PS/APP AD mouse model selectively decreases plaque load in the cortical region (Roltsch et al, 2010) and the overexpression of S100B increases Aβ levels and deposits, at early stages (Mori et al, 2010). Treatment of the 3XTg-AD mice with an antibody against IL-1 reduces S100B levels and results in attenuation of tau pathology and in partial reduction of certain fibrillar and oligomeric forms of Aβ (Kitazawa et al, 2011) S100B seems to be tied to different processes related to AD pathology as in addition to its ability to promote brain inflammatory response and tau pathology (Esposito et al, 2008b) it may play roles in directly promoting amyloidogenic APP processing, as proposed by Mori et al (2010).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
