The potential role of gut microbiota-derived metabolites as regulators of metabolic syndrome-associated mitochondrial and endolysosomal dysfunction in Alzheimer’s disease
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引用次数: 0
Abstract
Although the role of gut microbiota (GMB)-derived metabolites in mitochondrial and endolysosomal dysfunction in Alzheimer’s disease (AD) under metabolic syndrome remains unclear, deciphering these host–metabolite interactions represents a major public health challenge. Dysfunction of mitochondria and endolysosomal networks (ELNs) plays a crucial role in metabolic syndrome and can exacerbate AD progression, highlighting the need to study their reciprocal regulation for a better understanding of how AD is linked to metabolic syndrome. Concurrently, metabolic disorders are associated with alterations in the composition of the GMB. Recent evidence suggests that changes in the composition of the GMB and its metabolites may be involved in AD pathology. This review highlights the mechanisms of metabolic syndrome-mediated AD development, focusing on the interconnected roles of mitochondrial dysfunction, ELN abnormalities, and changes in the GMB and its metabolites. We also discuss the pathophysiological role of GMB-derived metabolites, including amino acids, fatty acids, other metabolites, and extracellular vesicles, in mediating their effects on mitochondrial and ELN dysfunction. Finally, this review proposes therapeutic strategies for AD by directly modulating mitochondrial and ELN functions through targeting GMB metabolites under metabolic syndrome. Although mitochondrial and endolysosomal network (ELN) impairment in metabolic syndrome is considered a risk factor for neurodegenerative diseases, the regulatory role of gut microbiota (GMB)-derived metabolites in this dysfunction remains unclear. This research explores the roles and molecular mechanisms of mitochondrial dysfunction, ELN abnormalities, dysregulation of mitochondria-ELN crosstalk, and changes in GMB and its metabolites in metabolic syndrome, especially in relation to Alzheimer’s disease (AD). The researchers conclude by highlighting the potential of targeting GMB and its metabolites to develop new AD treatments, especially for those with metabolic syndrome. They suggest that understanding and modulating the links between gut health, mitochondrial function, and ELN activity could lead to new management strategies for AD in the context of gut microbiota and its metabolites. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
期刊介绍:
Experimental & Molecular Medicine (EMM) stands as Korea's pioneering biochemistry journal, established in 1964 and rejuvenated in 1996 as an Open Access, fully peer-reviewed international journal. Dedicated to advancing translational research and showcasing recent breakthroughs in the biomedical realm, EMM invites submissions encompassing genetic, molecular, and cellular studies of human physiology and diseases. Emphasizing the correlation between experimental and translational research and enhanced clinical benefits, the journal actively encourages contributions employing specific molecular tools. Welcoming studies that bridge basic discoveries with clinical relevance, alongside articles demonstrating clear in vivo significance and novelty, Experimental & Molecular Medicine proudly serves as an open-access, online-only repository of cutting-edge medical research.