TY - JOUR
T1 - The Astrocytic S100B Protein with Its Receptor RAGE Is Aberrantly Expressed in SOD1(G93A) Models, and Its Inhibition Decreases the Expression of Proinflammatory Genes
AU - Serrano, A
AU - Donno, C
AU - Giannetti, Stefano
AU - Peric, M
AU - Andjus, P
AU - D'Ambrosi, N
AU - Michetti, F
PY - 2017
Y1 - 2017
N2 - Neuroinflammation is one of the major players in amyotrophic lateral sclerosis (ALS) pathogenesis, and astrocytes are significantly involved in this process. The astrocytic protein S100B can be released in pathological states activating the receptor for advanced glycation end products (RAGE). Different indications point to an aberrant expression of S100B and RAGE in ALS. In this work, we observed that S100B and RAGE are progressively and selectively upregulated in astrocytes of diseased rats with a tissue-specific timing pattern, correlated to the level of neurodegeneration. The expression of the full-length and soluble RAGE isoforms could also be linked to the degree of tissue damage. The mere presence of mutant SOD1 is able to increase the intracellular levels and release S100B from astrocytes, suggesting the possibility that an increased astrocytic S100B expression might be an early occurring event in the disease. Finally, our findings indicate that the protein may exert a proinflammatory role in ALS, since its inhibition in astrocytes derived from SOD1(G93A) mice limits the expression of reactivity-linked/proinflammatory genes. Thus, our results propose the S100B-RAGE axis as an effective contributor to the pathogenesis of the disease, suggesting its blockade as a rational target for a therapeutic intervention in ALS.
AB - Neuroinflammation is one of the major players in amyotrophic lateral sclerosis (ALS) pathogenesis, and astrocytes are significantly involved in this process. The astrocytic protein S100B can be released in pathological states activating the receptor for advanced glycation end products (RAGE). Different indications point to an aberrant expression of S100B and RAGE in ALS. In this work, we observed that S100B and RAGE are progressively and selectively upregulated in astrocytes of diseased rats with a tissue-specific timing pattern, correlated to the level of neurodegeneration. The expression of the full-length and soluble RAGE isoforms could also be linked to the degree of tissue damage. The mere presence of mutant SOD1 is able to increase the intracellular levels and release S100B from astrocytes, suggesting the possibility that an increased astrocytic S100B expression might be an early occurring event in the disease. Finally, our findings indicate that the protein may exert a proinflammatory role in ALS, since its inhibition in astrocytes derived from SOD1(G93A) mice limits the expression of reactivity-linked/proinflammatory genes. Thus, our results propose the S100B-RAGE axis as an effective contributor to the pathogenesis of the disease, suggesting its blockade as a rational target for a therapeutic intervention in ALS.
KW - N/A
KW - N/A
UR - https://publicatt.unicatt.it/handle/10807/172677
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85022228126&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85022228126&origin=inward
U2 - 10.1155/2017/1626204
DO - 10.1155/2017/1626204
M3 - Article
SN - 0962-9351
VL - 2017
SP - 26204
EP - 26204
JO - Mediators of Inflammation
JF - Mediators of Inflammation
IS - n.d
ER -