Scholarlink

Abstract <p>Parkinson’s disease (PD) is one of the most common neurodegenerativedisorders, characterized by the loss of dopaminergic neurons andthe accumulation of aggregated alpha-synuclein protein. The molecularmechanisms underlying PD pathogenesis remain largely unknown, sothere are no effective neuroprotective therapies to date. Meanwhile,recent research has identified a link between alpha-synuclein accumulationand aggregation, activation of type I interferon microglial responses,and subsequent neurodegeneration. STING (Stimulator of InterferonGenes) is a key protein regulator of innate immunity, responsiblefor the production of type I interferons and the orchestration of inflammatoryresponses. Upon activation, STING initiates signaling cascades thatregulate immune responses, cell death mechanisms, and autophagy.In the context of PD, STING hyperactivation may contribute to theprogression of neuroinflammation and associated neurodegeneration.Therefore, the development of STING inhibitors capable of modulatingits activity is considered a promising therapeutic strategy forPD. At the same time, given the multifunctionality of STING in cellular processes,a balance between its activity and therapeutic efficacy must beconsidered when developing PD therapies based on its inhibition.This balance could be achieved through combinatorial treatments involvingSTING inhibitors and compounds that reduce alpha-synuclein levels.This review discusses the structural features and activation mechanismsof STING, its role in the regulation of cell death and autophagy,as well as potential therapeutic strategies targeting this pathwayfor the development of novel treatments for PD, particularly itsform associated with mutations in the <i>GBA1</i> gene.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

STING Signaling Pathway as a Target for Neuroprotective Therapy in Parkinson’s Disease

  • 期刊论文

  • 发表日期：

    2025年5月1日

查看全文
  • T. S. Usenko

摘要

Abstract

Parkinson’s disease (PD) is one of the most common neurodegenerativedisorders, characterized by the loss of dopaminergic neurons andthe accumulation of aggregated alpha-synuclein protein. The molecularmechanisms underlying PD pathogenesis remain largely unknown, sothere are no effective neuroprotective therapies to date. Meanwhile,recent research has identified a link between alpha-synuclein accumulationand aggregation, activation of type I interferon microglial responses,and subsequent neurodegeneration. STING (Stimulator of InterferonGenes) is a key protein regulator of innate immunity, responsiblefor the production of type I interferons and the orchestration of inflammatoryresponses. Upon activation, STING initiates signaling cascades thatregulate immune responses, cell death mechanisms, and autophagy.In the context of PD, STING hyperactivation may contribute to theprogression of neuroinflammation and associated neurodegeneration.Therefore, the development of STING inhibitors capable of modulatingits activity is considered a promising therapeutic strategy forPD. At the same time, given the multifunctionality of STING in cellular processes,a balance between its activity and therapeutic efficacy must beconsidered when developing PD therapies based on its inhibition.This balance could be achieved through combinatorial treatments involvingSTING inhibitors and compounds that reduce alpha-synuclein levels.This review discusses the structural features and activation mechanismsof STING, its role in the regulation of cell death and autophagy,as well as potential therapeutic strategies targeting this pathwayfor the development of novel treatments for PD, particularly itsform associated with mutations in the GBA1 gene.