Hunjan Garry, Aran Khadga Raj
Department of Pharmacy Practice, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Moga, 142001, Punjab, India.
Inflammopharmacology. 2025 May 3. doi: 10.1007/s10787-025-01765-3.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterised by oxidative stress, mitochondrial dysfunction, synaptic impairment, and neuronal loss. The progression of AD depends on two main pathologic features, amyloid-beta accumulation, and tau pathology, whereas the disruption of glutamatergic neurotransmission plays an essential role in disease progression. Glutamate, the brain's primary excitatory neurotransmitter, acts on ionotropic and metabotropic glutamate receptors (mGluRs). Metabotropic glutamate receptor 7 (mGluR7) is a pre-synaptic type III mGluR receptor playing a crucial role in the central nervous system (CNS) through neurotransmitter modulation, reducing glutamate-induced excitotoxicity, and promoting early neuronal growth. Since mGluR7 is a key regulator of neurotransmitter release, it modulates synaptic integrity and neuronal survival, and its dysfunction is associated with impaired synaptic homeostasis in AD. Moreover, mGluR7 interacts with neuroinflammatory pathways by activating microglia and regulating cytokine production, therefore playing a significant role in AD pathogenesis. The drugs targeting mGluR7, including mGluR7 agonists, antagonists, and allosteric modulators, could potentially be among the most effective agents for the treatment of psychiatric disorders, neurodegenerative diseases including AD, as well as neurodevelopmental impairments, though these potential therapies remain in the early stages. This article summarises the structure as well as the function of mGluR7 and explores current insights into the functioning of mGluR7 in molecular mechanisms of AD pathogenesis. It also discusses potential therapeutic targets of mGluR7, highlighting the need to develop such therapies to prevent disease progression.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为氧化应激、线粒体功能障碍、突触损伤和神经元丢失。AD的进展取决于两个主要病理特征，即β-淀粉样蛋白积累和tau病理变化，而谷氨酸能神经传递的破坏在疾病进展中起关键作用。谷氨酸是大脑主要的兴奋性神经递质，作用于离子型和代谢型谷氨酸受体（mGluRs）。代谢型谷氨酸受体7（mGluR7）是一种突触前III型mGluR受体，通过神经递质调节、降低谷氨酸诱导的兴奋性毒性以及促进早期神经元生长，在中枢神经系统（CNS）中发挥关键作用。由于mGluR7是神经递质释放的关键调节因子，它调节突触完整性和神经元存活，其功能障碍与AD中突触稳态受损有关。此外，mGluR7通过激活小胶质细胞和调节细胞因子产生与神经炎症途径相互作用，因此在AD发病机制中起重要作用。靶向mGluR7的药物，包括mGluR7激动剂、拮抗剂和变构调节剂，可能是治疗精神疾病、包括AD在内的神经退行性疾病以及神经发育障碍最有效的药物之一，尽管这些潜在疗法仍处于早期阶段。本文总结了mGluR7的结构和功能，并探讨了目前对mGluR7在AD发病机制分子机制中功能的见解。还讨论了mGluR7的潜在治疗靶点，强调了开发此类疗法以预防疾病进展的必要性。
