Alzheimer's and Seizures: Interleukin-18, Indoleamine 2,3-Dioxygenase and Quinolinic Acid:

International Journal of Tryptophan Research

GAnderson¹ 

关键词: Alzheimer's;    seizures;    IL-18;    IDO;    melatonin;    microglia;    astrocytes;    losartan;   

DOI  :  10.4137/IJTR.S4603

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Emergent seizures are common in Alzheimer's disease (AD), although the mechanisms mediating this are unknown. It is proposed that stress induced interleukin-18 (IL-18), via interferon-gamma (IFNy) and independently, increases indoleamine 2,3-dioxygenase (IDO) and subsequent quinolinic acid (QA) in microglia. QA increases seizures and concurrently contributes to neuronal loss via excitotoxicity. The ApoE4 allele interacts with IL-18 polymorphisms to increase the risk of AD, and seems likely to potentiate the emergence of seizures. Concurrent changes in IDO and the kynurenine pathways at the blood-brain-barrier (BBB) have implications for treatment, including in the efficacy of different anti-hypertensives. Melatonin is proposed to inhibit these overlapping excitotoxic and neurodegenerative processes, and would be a useful adjunctive treatment.

【 授权许可】

CC BY