嘌呤受体与阿尔茨海默病及靶向药物的研究进展 ^*

Purinergic receptors in neurodegeneration: focus on Alzheimer's disease and targeted drug development

摘要

阿尔茨海默病 (AD) 是一种起病隐匿、进行性加重的神经退行性疾病。嘌呤受体在神经传递和神经调节中起关键作用, 参与 AD 的病理过程, 包括 β-淀粉样蛋白 (Aβ) 沉积、Tau 蛋白异常磷酸化、神经元丢失及反应性胶质细胞增生和神经炎症等。激活某些嘌呤受体可以通过保护神经元、清除 Aβ 斑块以及参与炎症反应等改善 AD 认知障碍; 抑制某些嘌呤受体则通过减少神经元突触可塑性损伤、Aβ 沉积、加快淀粉样前体蛋白水解及参与炎症反应等过程, 逆转 AD 的记忆缺陷。本文就嘌呤受体在 AD 病理改变中的机制及其相关靶向药物的研究进展作一综述, 以期为 AD 的治疗提供思路和参考。

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual onset and progressive deterioration. The purinergic signaling pathway is crucial for neurotransmission and neuromodulation, and is implicated in the pathogenic mechanisms of AD, encompassing amyloid β-protein (Aβ) accumulation, aberrant phosphorylation of Tau protein, oxidative stress (ROS), and persistent neuroinflammation. Activation of specific purine receptors can ameliorate cognitive deficits in AD by safeguarding neurons, eliminating Aβ plaques, and engaging in inflammatory responses. Inhibition of certain purine receptors ameliorates memory losses in AD by mitigating neuronal synaptic plasticity impairment, decreasing Aβ deposition, expediting amyloid precursor protein (APP) hydrolysis, and engaging in inflammatory responses. This article elucidates the role of purinergic receptors in the pathological alterations of AD and reviews the advancements in targeted pharmacological interventions, aiming to offer insights and references for AD treatment.

关键词

嘌呤受体 / 阿尔茨海默病 / β-淀粉样蛋白 / 靶向药物

Key words

Purinergic receptors / Alzheimer's disease / Amyloid β-protein / Targeted drugs

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基金资助

^*国家自然科学基金(82205284)

陕西中医药大学青年科技新星项目(2024-KJXX-02)