Human-Induced Pluripotent Stem Cells and Herbal Small-Molecule Drugs for Treatment of Alzheimer’s Disease

Abstract

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.

Comprehensive Bibliometric Analysis of Stem Cell Research in Alzheimer’s Disease from 2004 to 2022

“…Since a new method developed by Takahashi and Yamanaka in 2007, iPSCs have revolutionized neurological diseases modeling on account of eliminating ethical concerns and resolving the issue of immune rejection in stem cell transplantation [64, 65]. At the same time, the iPSC approach presents exceptional prospects for patient-specific medication screening and patient-specific patient studies [66–68]. It also reflects in the second stage, from 2009 onward, where the annual number of publications increases steadily and reaches 217 papers for the first time in 2015.…”

The Potential of Induced Pluripotent Stem Cells to Treat and Model Alzheimer’s Disease

“…This potential for successful reprogramming might be possible because the nervous system and ectoderm originate from the same embryonic tissue, the neuroectoderm [69]. These iPSCs can be transplanted into the region of interest (ROI) in the brain tissue of transgenic animal models, and the effects on different cognitive abilities can be observed, such as learning, memory, arousal, motor function, and motivational response [70]. However, as previously stated, higher-level cognitive abilities that are characteristic of certain neurodegenerative diseases are difficult to study, even with the addition of iPSC technology in transgenic animal models.…”

“…Mutations of PSEN1/2, the catalytic component of γsecretase, have been linked to familial Alzheimer's disease (fAD). Patients with fAD have mutations in PSEN1 (A246E) and PSEN2 (N141I) [70]. A separate PSEN1 exon 9 deletion (PSEN1δ9) produced mutant astrocytes that altered the calcium signaling activity of healthy neurons when AD astrocytes generated from iPSC from PSEN1δ9 donor cells were cocultured with healthy neurons [128].…”

The Role of Beta-Amyloid in Norm and at Alzheimer`s Disease

“…Внаслідок мутації генів цієї системи або інших факторів, може відбуватися неправильне розщеплення і утворюються пептидні фрагменти, які важко метаболізуються (1-40 ~ 1-42 амінокислоти). Позначення: PSEN1 -пресенілін-1; PSEN2 -пресенілін-2; BACE1 -β-секретаза-1; APP-білок-попередник амілоїду [55] Рис. 2.…”