bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2022‒12‒25
six papers selected by
Mikaila Chetty
Goa University

  1. Antioxidants (Basel). 2022 Dec 15. pii: 2467. [Epub ahead of print]11(12):
      Parkinson's disease (PD) is a gradually progressing neurodegenerative condition that is marked by a loss of motor coordination along with non-motor features. Although the precise cause of PD has not been determined, the disease condition is mostly associated with the exposure to environmental toxins, such as metals, and their abnormal accumulation in the brain. Heavy metals, such as iron (Fe), mercury (Hg), manganese (Mn), copper (Cu), and lead (Pb), have been linked to PD and contribute to its progression. In addition, the interactions among the components of a metal mixture may result in synergistic toxicity. Numerous epidemiological studies have demonstrated a connection between PD and either single or mixed exposure to these heavy metals, which increase the prevalence of PD. Chronic exposure to heavy metals is related to the activation of proinflammatory cytokines resulting in neuronal loss through neuroinflammation. Similarly, metals disrupt redox homeostasis while inducing free radical production and decreasing antioxidant levels in the substantia nigra. Furthermore, these metals alter molecular processes and result in oxidative stress, DNA damage, mitochondrial dysfunction, and apoptosis, which can potentially trigger dopaminergic neurodegenerative disorders. This review focuses on the roles of Hg, Pb, Mn, Cu, and Fe in the development and progression of PD. Moreover, it explores the plausible roles of heavy metals in neurodegenerative mechanisms that facilitate the development of PD. A better understanding of the mechanisms underlying metal toxicities will enable the establishment of novel therapeutic approaches to prevent or cure PD.
    Keywords:  Parkinson’s disease; copper; heavy metals; iron; lead; manganese; mercury; oxidative stress
  2. Ageing Res Rev. 2022 Dec 19. pii: S1568-1637(22)00270-7. [Epub ahead of print] 101828
      Alzheimer's disease (AD) is the most common form of dementia and seriously affects the quality of life of the elderly. Neurodegeneration is closely related to hippocampal dysfunction in AD patients. The hippocampus is key to creating new memories and is also one of the first areas of the brain to deteriorate with age. Mammalian neurogenesis occurs mainly in the hippocampus. Recent studies have confirmed that neurogenesis in the hippocampus is sustainable but decreases with age, which seriously affects the learning and memory function of AD patients. At present, our understanding of neurogenesis is still relatively shallow, especially pertaining to the influence and role of neurogenesis during aging and cognitive deficits in AD patients. Interestingly, many recent studies have described the characteristics of neurogenesis in animal models. This article reviews the progress of neurogenesis research in the context of aging and AD to provide new insights into neurogenesis.
    Keywords:  Adults; Aging; Alzheimer's disease; Learning and memory; Neurogenesis
  3. Biol Trace Elem Res. 2022 Dec 19.
      Magnesium is an essential cation present in the body that participates in the regulation of various vital body functions. Maintaining normal level of magnesium is essential for proper brain functions by regulating the activities of numerous neurotransmitters and their receptors. Various studies have been reported that magnesium level is found to be declined in both neurological and psychiatric diseases. Declined magnesium level in the brain initiates various cumbersome effects like excitotoxicity, altered blood-brain permeability, oxidative stress, and inflammation, which may further worsen the disease condition. Shreds of evidence from the experimental and clinical studies proved that exogenous administration of magnesium is useful for correcting disease-induced alterations in the brain. But one of the major limiting factors in the use of magnesium for treatment purposes is its poor blood-brain barrier permeability. Various approaches like the administration of its organic salts as pidolate and threonate forms, and the combination with polyethylene glycol or mannitol have been tried to improve its permeability to make magnesium as a suitable drug for different neurological disorders. These results have shown their experimental efficacy in diseased animal models, but studies regarding the safety and efficacy in human subjects are currently underway. We present a comprehensive review on the role of magnesium in the maintenance of normal functioning of the brain and various approaches for improving its BBB permeability.
    Keywords:  Blood–brain barrier; Hypomagnesemia; Magnesium; Magnesium deficiency; Neurological disorders; Psychiatric diseases
  4. Nutrients. 2022 Dec 10. pii: 5269. [Epub ahead of print]14(24):
      Gestational diabetes mellitus (GDM) is one of the most common obstetric complications due to an increased level of glucose intolerance during pregnancy. The prevalence of GDM increases due to the obesity epidemic. GDM is also associated with an increased risk of gestational hypertension and preeclampsia resulting in elevated maternal and perinatal morbidity and mortality. Diet is one of the most important environmental factors associated with etiology of GDM. Studies have shown that the consumption of certain bioactive diets and nutrients before and during pregnancy might have preventive effects against GDM leading to a healthy pregnancy outcome as well as beneficial metabolic outcomes later in the offspring's life. Gut microbiome as a biological ecosystem bridges the gap between human health and diseases through diets. Maternal diets affect maternal and fetal gut microbiome and metabolomics profiles, which consequently regulate the host epigenome, thus contributing to later-life metabolic health in both mother and offspring. This review discusses the current knowledge regarding how epigenetic mechanisms mediate the interaction between maternal bioactive diets, the gut microbiome and the metabolome leading to improved metabolic health in both mother and offspring.
    Keywords:  epigenome; gestational diabetes; maternal diets; metabolome; microbiome
  5. Diseases. 2022 Dec 01. pii: 117. [Epub ahead of print]10(4):
      Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease, the pathogenesis of which is based on alternations in the mitochondria of motor neurons, causing their progressive death. A growing body of evidence shows that more efficient mitophagy could prevent and/or treat this disorder by suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. Mitophagy has been considered one of the main mechanisms responsible for mitochondrial quality control. Since ALS is characterized by enormous oxidative stress, several edible phytochemicals that can activate mitophagy to remove damaged mitochondria could be considered a promising option to treat ALS by providing neuroprotection. Therefore, it is of great significance to explore the mechanisms of mitophagy in ALS and to understand the effects and/or molecular mechanisms of phytochemical action, which could translate into a treatment for neurodegenerative diseases, including ALS.
    Keywords:  ALS; AMPK; ROS; mTOR; mTORC1; mitophagy; natural product
  6. EFSA J. 2022 Dec;20(Suppl 2): e200915
      This work explores three areas of relevance to the gut microbiome in the context of One Health; the incorporation of the microbiome in food safety risk assessment of xenobiotics; the identification and application of beneficial microbial components to various areas under One Health, and specifically, in the context of antimicrobial resistance. We conclude that, although challenging, focusing on the microbiota resilience, function and active components, are critical for advancing the incorporation of the gut microbiome in the risk assessment of xenobiotics. Moreover, research technologies, such as toxicomicrobiomics, culturomics and genomics, especially in combination, have revealed that the human microbiota may be a promising source of beneficial taxa or other components, with the potential to metabolise and biodegrade xenobiotics. These may have possible applications in several health areas, including in animals or plants for detoxification or in the environment for bioremediation. This approach would be of particular interest for antimicrobials, with the potential to ameliorate antimicrobial resistance development. Finally, we propose that the concept of resistance to xenobiotics in the context of the gut microbiome may deserve further investigation in the pursuit of holistically elucidating their involvement in the balance between health and disease.
    Keywords:  One Health; antimicrobial resistance; gut microbiome; microbiota‐disrupting chemicals; next‐generation probiotics; next‐generation risk assessment; xenobiotics