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bioRxiv · 10.1101/2023.04.03.535377

Increased Cerebral Serum Amyloid A2 and Parameters of Oxidation in Arylsulfatase B (N-Acetylgalactosamine-4-Sulfatase)-Null Mice

Tobacman, J. K.·Bhattacharyya, S.
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Abstract

IntroductionChondroitin sulfate and chondroitin sulfate proteoglycans have been associated with Alzheimers Disease (AD), and the impact of modified chondroitin sulfates is being investigated in several animal and cell-based models of AD. Published reports have shown the role of accumulation of chondroitin 4-sulfate and decline in Arylsulfatase B (ARSB; B-acetylgalactosamine-4-sulfatase) in other pathology, including nerve injury, traumatic brain injury, and spinal cord injury. However, the impact of ARSB deficiency on AD pathobiology has not been reported, although changes in ARSB were associated with AD in two prior reports. The enzyme ARSB removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate and dermatan sulfate and is required for their degradation. When ARSB activity declines, these sulfated glycosaminoglycans accumulate, as in the inherited disorder Mucopolysaccharidosis VI. MethodsReports about chondroitin sulfate, chondroitin sulfate proteoglycans and chondroitin sulfatases in Alzheimers Disease were reviewed. Measurements of SAA2, iNOS, lipid peroxidation, chondroitin sulfate proteoglycan 4, and other parameters were performed in cortex and hippocampus from ARSB-null mice and controls by QRT-PCR, ELISA, and other standard assays. ResultsSAA2 mRNA expression and protein, CSPG4 mRNA, chondroitin 4-sulfate and i-NOS were increased significantly in ARSB-null mice. Measures of lipid peroxidation and redox state were significantly modified. DiscussionFindings indicate that decline in ARSB leads to changes in expression of parameters associated with AD in the hippocampus and cortex of the ARSB-deficient mouse. ConclusionsFurther investigation of the impact of decline in ARSB on the development of AD may provide a new approach to prevent and treat AD.

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Tobacman, J. K., Bhattacharyya, S.. 2023-04-03. Increased Cerebral Serum Amyloid A2 and Parameters of Oxidation in Arylsulfatase B (N-Acetylgalactosamine-4-Sulfatase)-Null Mice. https://doi.org/10.1101/2023.04.03.535377

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