Recent studies indicate the involvement of glycosylation in the pathogenesis of Alzheimer's disease(AD).a2,6-Sialylation,catalyzed by a2,6-sialyltransferase-I(ST6Gal-I),corresponds to the development of the infant...Recent studies indicate the involvement of glycosylation in the pathogenesis of Alzheimer's disease(AD).a2,6-Sialylation,catalyzed by a2,6-sialyltransferase-I(ST6Gal-I),corresponds to the development of the infant brain and nervous system,however the mechanism of aberrant a2,6-sialylation affects multiple physiological and pathological conditions remains unclear.The present study,in vitro and in vivo,showed that expression of ST6Gal-I and a2,6-sialylation levels were up-regulated in cerebrospinal fluid and sera of AD patients.In addition,levels of a2,6-sialylation were also increased in brain and sera of AD model mice.Furthermore,deletion of ST6Gal-I reduced β-site amyloid precursor protein cleaving enzyme 1(BACE1)levels and alleviated the impairment of learning and memory induced by scopolamine in rats.BACE1,a hyper-sialylated protein,plays a critical role in amyloid-β_(42)(Aβ_(42))production.ST6Gal-I knockdown in Neuro-2a neuroblastoma cells(ST6Gal-I-KD-N2a)reduced the expression of BACE1 via promoting its ubiquitination.Deletion of ST6Gal-I suppressed amyloid precursor protein(APP)cleaved by BACE1,followed by a decrease in Aβ_(42)production,while alleviated Aβ_(42)-induced apoptosis.This study first reveals a significant role of a2,6-sialylation in development and progression of AD,suggesting that ST6Gal-I is a novel glycan therapeutic target for AD diagnosis and treatment.展开更多
基金supported by grants from the National Natural Science Foundation of China (32171279)the Guangdong Basic and Applied Basic Research Foundation (2024A1515012796)+1 种基金the Scientific Research Initiation Grant from Shantou University Medical College (510858066)the Provincial Science and Technology Innovation Strategy Special City and County Science and Technology Innovation Support Project (STKJ2023008)。
文摘Recent studies indicate the involvement of glycosylation in the pathogenesis of Alzheimer's disease(AD).a2,6-Sialylation,catalyzed by a2,6-sialyltransferase-I(ST6Gal-I),corresponds to the development of the infant brain and nervous system,however the mechanism of aberrant a2,6-sialylation affects multiple physiological and pathological conditions remains unclear.The present study,in vitro and in vivo,showed that expression of ST6Gal-I and a2,6-sialylation levels were up-regulated in cerebrospinal fluid and sera of AD patients.In addition,levels of a2,6-sialylation were also increased in brain and sera of AD model mice.Furthermore,deletion of ST6Gal-I reduced β-site amyloid precursor protein cleaving enzyme 1(BACE1)levels and alleviated the impairment of learning and memory induced by scopolamine in rats.BACE1,a hyper-sialylated protein,plays a critical role in amyloid-β_(42)(Aβ_(42))production.ST6Gal-I knockdown in Neuro-2a neuroblastoma cells(ST6Gal-I-KD-N2a)reduced the expression of BACE1 via promoting its ubiquitination.Deletion of ST6Gal-I suppressed amyloid precursor protein(APP)cleaved by BACE1,followed by a decrease in Aβ_(42)production,while alleviated Aβ_(42)-induced apoptosis.This study first reveals a significant role of a2,6-sialylation in development and progression of AD,suggesting that ST6Gal-I is a novel glycan therapeutic target for AD diagnosis and treatment.
