In recent years, the incidence of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, has shown a steadily rising trend, which has posed a major challenge to the global public health. Traditional Chinese Medicine (TCM), with its multi-component and multi-target characteristics, offers a promising approach for the treatment of neurodegenerative diseases. However, it is difficult to comprehensively elucidate the complex mechanisms underlying TCM formulations. As an emerging systems biology approach, network pharmacology has provided a crucial tool for uncovering the multi-target mechanisms of TCM through high-throughput technologies, molecular docking, and network analysis. This paper reviews the advancements in the application of network pharmacology in treating neurodegenerative diseases with TCM, analyzes the current status of relevant databases and technological methods, discusses the limitations in the research, and proposes future directions to promote the modernization of TCM and the development of precision medicine. Keywords: Neurodegenerative diseases, Traditional Chinese Medicine, Network pharmacology, Therapeutic targets.
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http://dx.doi.org/10.1055/a-2512-8928 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
Background: Astrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer's disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub-types most associated with these diseases are now reported to be present during CNS cancers of several types.
View Article and Find Full Text PDFBackground: The hyperphosphorylation, mislocalization, and aggregation of the microtubule associated protein Tau (MAPT) is a driving force in tauopathies, a group of progressive, neurodegenerative disorders. These pathogenic intracellular aggregates, known as neurofibrillary tangles (NFTs), are a hallmark in several diseases such as frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's Disease. While anti-Tau immunotherapies emphasize the clearance of extracellular Tau aggregates, they do not address the intracellular accumulation of NFTs.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
ADEL Institute of Science & Technology (AIST), ADEL, Inc., Seoul, Korea, Republic of (South).
Background: The spatiotemporal pattern of the spread of pathologically modified tau through brain regions in Alzheimer's disease (AD) can be explained by prion-like cell-to-cell seeding and propagation of misfolded tau aggregates. Hence, to develop targeted therapeutic antibodies, it is important to identify the seeding- and propagation-competent tau species. The hexapeptide VQIINK of tau is a critical region for tau aggregation, and K280 is acetylated in various tauopathies including AD.
View Article and Find Full Text PDFBackground: DYRK1A overexpression, common in neurodegenerative diseases like Alzheimer's (AD), contributes to neurofibrillary tangles via Tau protein hyperphosphorylation and amyloid plaque formation, key AD hallmarks. Therefore, DYRK1A has been regarded as a novel target for neurodegenerative diseases. However, developing DYRK1A selective inhibitors has been a difficult challenge due to the highly conserved ATP-binding site of protein kinases, particularly among the CMGC family.
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