bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2023‒05‒21
six papers selected by
Mikaila Chetty
Goa University

  1. Aging Dis. 2023 Jun 01. 14(3): 964-1678
      Alzheimer's disease (AD) is a degenerative disease of the central nervous system. The pathogenesis of AD has been explained using cholinergic, β-amyloid toxicity, tau protein hyperphosphorylation, and oxidative stress theories. However, an effective treatment method has not been developed. In recent years, with the discovery of the brain-gut axis (BGA) and breakthroughs made in Parkinson's disease, depression, autism, and other diseases, BGA has become a hotspot in AD research. Several studies have shown that gut microbiota can affect the brain and behavior of patients with AD, especially their cognitive function. Animal models, fecal microbiota transplantation, and probiotic intervention also provide evidence regarding the correlation between gut microbiota and AD. This article discusses the relationship and related mechanisms between gut microbiota and AD based on BGA to provide possible strategies for preventing or alleviating AD symptoms by regulating gut microbiota.
  2. Biomedicines. 2023 Apr 09. pii: 1131. [Epub ahead of print]11(4):
      Nonenzymatic reactions of reducing sugars with primary amino groups of amino acids, proteins, and nucleic acids, followed by oxidative degradations would lead to the formation of advanced glycation endproducts (AGEs). The AGEs exert multifactorial effects on cell damage leading to the onset of neurological disorders. The interaction of AGEs with the receptors for advanced glycation endproducts (RAGE) contribute to the activation of intracellular signaling and the expression of the pro-inflammatory transcription factors and various inflammatory cytokines. This inflammatory signaling cascade is associated with various neurological diseases, including Alzheimer's disease (AD), secondary effects of traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and diabetic neuropathy, and other AGE-related diseases, including diabetes and atherosclerosis. Furthermore, the imbalance of gut microbiota and intestinal inflammation are also associated with endothelial dysfunction, disrupted blood-brain barrier (BBB) and thereby the onset and progression of AD and other neurological diseases. AGEs and RAGE play an important role in altering the gut microbiota composition and thereby increase the gut permeability and affect the modulation of the immune-related cytokines. The inhibition of the AGE-RAGE interactions, through small molecule-based therapeutics, prevents the inflammatory cascade of events associated with AGE-RAGE interactions, and thereby attenuates the disease progression. Some of the RAGE antagonists, such as Azeliragon, are currently in clinical development for treating neurological diseases, including AD, although currently there have been no FDA-approved therapeutics based on the RAGE antagonists. This review outlines the AGE-RAGE interactions as a leading cause of the onset of neurological diseases and the current efforts on developing therapeutics for neurological diseases based on the RAGE antagonists.
    Keywords:  AGEs; Alzheimer’s disease; RAGE; RAGE antagonists; cytokines; glycation; oxidative stress; soluble RAGE; traumatic brain injury
  3. Front Neurosci. 2023 ;17 1130730
      Being isolated from the peripheral system by the blood-brain barrier, the brain has long been considered a completely impervious tissue. However, recent findings show that the gut microbiome (GM) influences gastrointestinal and brain disorders such as Alzheimer's disease (AD). Despite several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, and oxidative stress, being proposed to explain the origin and progression of AD, the pathogenesis remains incompletely understood. Epigenetic, molecular, and pathological studies suggest that GM influences AD development and have endeavored to find predictive, sensitive, non-invasive, and accurate biomarkers for early disease diagnosis and monitoring of progression. Given the growing interest in the involvement of GM in AD, current research endeavors to identify prospective gut biomarkers for both preclinical and clinical diagnoses, as well as targeted therapy techniques. Here, we discuss the most recent findings on gut changes in AD, microbiome-based biomarkers, prospective clinical diagnostic uses, and targeted therapy approaches. Furthermore, we addressed herbal components, which could provide a new venue for AD diagnostic and therapy research.
    Keywords:  Alzheimer’s disease; biomarkers; gut microbiome; microbiome-gut-brain axis; traditional Chinese medicine
  4. Front Physiol. 2023 ;14 1114231
      Mitochondria play a key role in both health and disease. Their function is not limited to energy production but serves multiple mechanisms varying from iron and calcium homeostasis to the production of hormones and neurotransmitters, such as melatonin. They enable and influence communication at all physical levels through interaction with other organelles, the nucleus, and the outside environment. The literature suggests crosstalk mechanisms between mitochondria and circadian clocks, the gut microbiota, and the immune system. They might even be the hub supporting and integrating activity across all these domains. Hence, they might be the (missing) link in both health and disease. Mitochondrial dysfunction is related to metabolic syndrome, neuronal diseases, cancer, cardiovascular and infectious diseases, and inflammatory disorders. In this regard, diseases such as cancer, Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), chronic fatigue syndrome (CFS), and chronic pain are discussed. This review focuses on understanding the mitochondrial mechanisms of action that allow for the maintenance of mitochondrial health and the pathways toward dysregulated mechanisms. Although mitochondria have allowed us to adapt to changes over the course of evolution, in turn, evolution has shaped mitochondria. Each evolution-based intervention influences mitochondria in its own way. The use of physiological stress triggers tolerance to the stressor, achieving adaptability and resistance. This review describes strategies that could recover mitochondrial functioning in multiple diseases, providing a comprehensive, root-cause-focused, integrative approach to recovering health and treating people suffering from chronic diseases.
    Keywords:  hormesis; mitochondria; mitochondrial dysfunction; mitochondrial hormesis; mitochondrial metabolism
  5. Biomedicines. 2023 Mar 29. pii: 1048. [Epub ahead of print]11(4):
      Taurine, an abundant free amino acid, plays multiple roles in the body, including bile acid conjugation, osmoregulation, oxidative stress, and inflammation prevention. Although the relationship between taurine and the gut has been briefly described, the effects of taurine on the reconstitution of intestinal flora homeostasis under conditions of gut dysbiosis and underlying mechanisms remain unclear. This study examined the effects of taurine on the intestinal flora and homeostasis of healthy mice and mice with dysbiosis caused by antibiotic treatment and pathogenic bacterial infections. The results showed that taurine supplementation could significantly regulate intestinal microflora, alter fecal bile acid composition, reverse the decrease in Lactobacillus abundance, boost intestinal immunity in response to antibiotic exposure, resist colonization by Citrobacter rodentium, and enhance the diversity of flora during infection. Our results indicate that taurine has the potential to shape the gut microbiota of mice and positively affect the restoration of intestinal homeostasis. Thus, taurine can be utilized as a targeted regulator to re-establish a normal microenvironment and to treat or prevent gut dysbiosis.
    Keywords:  Citrobacter rodentium; antibiontic; dysbiosis; gut microbiota; taurine
  6. Adv Virus Res. 2023 ;pii: S0065-3527(23)00004-0. [Epub ahead of print]115 135-158
      Viruses continue to pose a public health threat raising the need for effective management strategies. Currently existing antiviral therapeutics are often specific to only a single viral species, and resistance to the therapeutic can often arise, and therefore new therapeutics are needed. The C. elegans-Orsay virus system offers a powerful platform for studying RNA virus-host interactions that could ultimately lead to novel targets for antiviral therapy. The relative simplicity of C. elegans, the well-established experimental tools, and its extensive evolutionary conservation of genes and pathways with mammals are key features of this model. Orsay virus, a bisegmented positive sense RNA virus, is a natural pathogen of C. elegans. Orsay virus infection can be studied in a multicellular organismal context, overcoming some of the limitations inherent to tissue culture-based systems. Moreover, compared to mice, the rapid generation time of C. elegans enables robust and facile forward genetics. This review aims to summarize studies that have laid the foundation for the C. elegans-Orsay virus experimental system, experimental tools, and key examples of C. elegans host factors that impact Orsay virus infection that have evolutionarily conserved function in mammalian virus infection.
    Keywords:  Antiviral RNAi; Caenorhabditis elegans; Host factors; Innate immunity; Orsay virus