Hudák Anett, Letoha Tamás
Pharmacoidea Ltd., 6726 Szeged, Hungary.
Doctoral School of Theoretical Medicine, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary.
Int J Mol Sci. 2025 Apr 24;26(9):4037. doi: 10.3390/ijms26094037.
Alzheimer's disease and other neurodegenerative disorders are characterized by the accumulation of misfolded proteins, such as amyloid-beta, tau, and α-synuclein, which disrupt neuronal function and contribute to cognitive decline. Heparan sulfate proteoglycans, particularly syndecans, play a pivotal role in the seeding, aggregation, and spreading of toxic protein aggregates through endocytic pathways. Among these, syndecan-3 is particularly critical in regulating the internalization of misfolded proteins, facilitating their propagation in a prion-like manner. This review examines the mechanisms by which syndecans, especially SDC3, contribute to the seeding and spreading of pathological protein aggregates in neurodegenerative diseases. Understanding these endocytic pathways provides valuable insights into the potential of syndecans as biomarkers and therapeutic targets for early intervention in Alzheimer's disease and other related neurodegenerative disorders.
阿尔茨海默病和其他神经退行性疾病的特征是错误折叠蛋白的积累，如β-淀粉样蛋白、tau蛋白和α-突触核蛋白，这些蛋白会破坏神经元功能并导致认知能力下降。硫酸乙酰肝素蛋白聚糖，特别是多功能蛋白聚糖，在有毒蛋白质聚集体通过内吞途径的种子形成、聚集和扩散中起关键作用。其中，多功能蛋白聚糖-3在调节错误折叠蛋白的内化方面尤为关键，以朊病毒样方式促进其传播。这篇综述探讨了多功能蛋白聚糖，尤其是SDC3，在神经退行性疾病中促进病理性蛋白质聚集体的种子形成和扩散的机制。了解这些内吞途径为多功能蛋白聚糖作为生物标志物的潜力以及对阿尔茨海默病和其他相关神经退行性疾病进行早期干预的治疗靶点提供了有价值的见解。
