Presenilin-1 (PSEN1) is a crucial subunit within the γ-secretase complex and regulates β-amyloid (Aβ) production. Accumulated evidence indicates that n-butylidenephthalide (BP) acts effectively to reduce Aβ levels in neuronal cells that are derived from trisomy 21 (Ts21) induced pluripotent stem cells (iPSCs). However, the mechanism underlying this effect remains unclear. This article aims to investigate the possible mechanisms through which BP ameliorates the development of Alzheimer’s disease (AD) and verify the effectiveness of BP through animal experiments. Results from RNA microarray analysis showed that BP treatment in Ts21 iPSC-derived neuronal cells reduced long noncoding RNA (lncRNA) CYP3A43-2 levels and increased microRNA (miR)-29b-2-5p levels. Bioinformatics tool prediction analysis, biotin-labeled miR-29b-2-5p pull-down assay, and dual-luciferase reporter assay confirmed a direct negative regulatory effect for miRNA29b-2-5p on lnc-RNA-CYP3A43-2 and PSEN1. Moreover, BP administration improved short-term memory and significantly reduced Aβ accumulation in the hippocampus and cortex of 3xTg-AD mice but failed in miR-29b-2-5p mutant mice generated by CRISP/Cas9 technology. In addition, analysis of brain samples from patients with AD showed a decrease in microRNA-29b-2-5p expression in the frontal cortex region. Our results provide evidence that the LncCYP3A43-2/miR29-2-5p/PSEN1 network might be involved in the molecular mechanisms underlying BP-induced Aβ reduction.
Alzheimer's disease (AD) is a neurodegenerative disease with a variety of causes. Traditional Chinese medicine (TCM), which includes the two main approaches of acupuncture and herbal medication, views the human body as a self-controlled system network. Fundamental theories, including “qi,” the five elements, and the theory of viscera, form the basis for classification. Diseases in humans are considered to be caused by an imbalance of “yang qi” and “yin qi” that lead to the nonhomeostasis of organs. Acupuncture is derived from 12 main meridians and 365 acupuncture points characterized by “blood and qi.” Needling of different positions corresponds to specific disease treatments to increase qi. Treatment with Chinese herbal medicines is based on syndrome differentiation characterized as “Zheng” which differs from the cause orientation approach of Western medicine. In this article, we review basic and clinical research studies that describe TCM herbs and acupuncture for the treatment of AD. Moreover, we propose that these two approaches be integrated to improve the outcomes for AD patients.
Alzheimer’s disease (AD) is characterized by extracellular amyloid plaques composed of the β-amyloid peptides and intracellular neurofibrillary tangles and associates with progressive declines in memory and cognition. Several genes play important roles and regulate enzymes that produce a pathological accumulation of β-amyloid in the brain, such as gamma secretase (γ-secretase). Induced pluripotent stem cells from patients with Alzheimer’s disease with different underlying genetic mechanisms may help model different phenotypes of Alzheimer’s disease and facilitate personalized drug screening platforms for the identification of small molecules. We also discuss recent developments by γ-secretase inhibitors and modulators in the treatment of AD. In addition, small-molecule drugs isolated from Chinese herbal medicines have been shown effective in treating Alzheimer’s disease. We propose a mechanism of small-molecule drugs in treating Alzheimer’s disease. Combining therapy with different small-molecule drugs may increase the chance of symptomatic treatment. A customized strategy tailored to individuals and in combination with therapy may be a more suitable treatment option for Alzheimer’s disease in the future.
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