bims-metalz Biomed News
on Metabolic causes of Alzheimer’s disease
Issue of 2023–11–05
twelve papers selected by
Mikaila Chetty, Goa University
  1. Amyloid-beta and tau protein beyond Alzheimer's disease.
  2. The mechanisms and roles of mitochondrial dynamics in C. elegans.
  3. Comparative oxidative damages induced by silver nanoparticles with different sizes and coatings in Caenorhabditis elegans.
  4. Hesperidin ameliorates Amyloid-β toxicity and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans through acr-16 mediated activation of the autophagy pathway.
  5. A Multisystemic Approach Revealed Aminated Polystyrene Nanoparticles-Induced Neurotoxicity.
  6. Crucial physicochemical factors mediating mitochondrial toxicity of nanoparticles at noncytotoxic concentration.
  7. Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond.
  8. UNC-49 is a redox-sensitive GABAA receptor that regulates the mitochondrial unfolded protein response cell nonautonomously.
  9. Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson's disease.
  10. Flavonoids: Their putative neurologic roles, epigenetic changes, and gut microbiota alterations in Parkinson's disease.
  11. Coordination chemistry of mitochondrial copper metalloenzymes: exploring implications for copper dyshomeostasis in cell death.
  12. Secondary Protein Aggregates in Neurodegenerative Diseases: Almost the Rule Rather than the Exception.
  1. Neural Regen Res. 2024 Jun 01. 19(6): 1262-1276
    Amyloid-beta and tau protein beyond Alzheimer's disease.
    Morteza Abyadeh, Vivek Gupta, Joao A Paulo, Arezoo Gohari Mahmoudabad, Sina Shadfar, Shahab Mirshahvaladi, Veer Gupta, Christine T O Nguyen, David I Finkelstein, Yuyi You, Paul A Haynes, Ghasem H Salekdeh, Stuart L Graham, Mehdi Mirzaei.
       ABSTRACT: The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer's disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, post-translational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.
    DOI:  https://doi.org/10.4103/1673-5374.386406
  2. Semin Cell Dev Biol. 2023 Oct 31. pii: S1084-9521(23)00203-3. [Epub ahead of print]
    The mechanisms and roles of mitochondrial dynamics in C. elegans.
    Daniel Campbell, Steven Zuryn.
      If mitochondria are the powerhouses of the cell, then mitochondrial dynamics are the power grid that regulates how that energy output is directed and maintained in response to unique physiological demands. Fission and fusion dynamics are highly regulated processes that fine-tune the mitochondrial networks of cells to enable appropriate responses to intrinsic and extrinsic stimuli, thereby maintaining cellular and organismal homeostasis. These dynamics shape many aspects of an organism's healthspan including development, longevity, stress resistance, immunity, and response to disease. In this review, we discuss the latest findings regarding the mechanisms and roles of mitochondrial dynamics by focussing on the nematode Caenorhabditis elegans. Whole live-animal studies in C. elegans have enabled a true organismal-level understanding of the impact that mitochondrial dynamics play in homeostasis over a lifetime.
    Keywords:  Development; Disease; Fission; Fusion; Longevity; Quality-control
    DOI:  https://doi.org/10.1016/j.semcdb.2023.10.006
  3. Toxicol Res (Camb). 2023 Oct;12(5): 833-842
    Comparative oxidative damages induced by silver nanoparticles with different sizes and coatings in Caenorhabditis elegans.
    Shuyan Niu, Junjun Wang, Xiaoru Chang, Mengting Shang, Menghao Guo, Zuoyi Sun, Yunjing Li, Yuying Xue.
      Silver nanoparticles (AgNPs) are widely used in many commercial and medical products. Serious concerns are paid on their adverse potentials to the environment and human health. In this study, toxic effects and oxidative stress induced by AgNPs with different sizes and coatings (20 nm AgNPs, 20 nm polyvinylpyrrolidone (PVP) -AgNPs and 50 nm AgNPs) in Caenorhabditis elegans (C. elegans) were investigated. The toxic effects including the shortened lifespan and decreased frequency of head thrashes and body bends of C. elegans were induced in a dose-dependent manner by AgNPs. The reactive oxygen species (ROS) production and the oxidative stress-related indicators including malondialdehyde (MDA) and glutathione (GSH) in nematodes were changed after exposure to three kinds of AgNPs. These effects were the most obvious in a 20 nm PVP-AgNPs exposure group. AgNPs could also induce the expression of genes related to oxidative stress in nematodes. In addition, the up-regulation of mtl-1 and mtl-2 in nematodes might reduce the oxidative damage caused by AgNPs, by using transgenic strains CF2222 and CL2120 nematodes. Metallothionein (MT), an antioxidant, could relieve the oxidative damage caused by AgNPs. These results suggested that 20 nm PVP-AgNPs with a smaller particle size and better dispersion have stronger toxic effects and the oxidative damage to nematodes. Mtl-1 and mtl-2 might be involved in alleviating the oxidative damage caused by AgNPs. Our findings provide clues for the safety evaluation and mechanism information of metal nanoparticles.
    Keywords:  caenorhabditis elegans; metallothionein; nanotoxicity; oxidative stress; silver nanoparticles
    DOI:  https://doi.org/10.1093/toxres/tfad074
  4. Free Radic Biol Med. 2023 Oct 30. pii: S0891-5849(23)01086-9. [Epub ahead of print]
    Hesperidin ameliorates Amyloid-β toxicity and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans through acr-16 mediated activation of the autophagy pathway.
    Sandeep Kumar, P V Akhila, Kitlangki Suchiang.
      Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in aged populations. Aberrant amyloid-beta accumulation is a common pathological feature in AD patients. Dysfunction of autophagy and impairment of α7nAChR functioning are associated with enhanced amyloid-beta (Aβ) accumulation in AD patients. Hesperidin, a flavone glycoside found primarily in citrus species, is known to have anti-inflammatory, antioxidant, and neuroprotective effects. However, the underlying molecular mechanisms of hesperidin as an antiaging and anti-Aβ phytochemical were unclear. In this study, we found that hesperidin upregulates the acr-16 expression level in C. elegans as evidenced by increased GFP-tagged ACR-16 and GFP-tagged pmyo-3:ACR-16 expression in muscle and ventral cord. Further, hesperidin upregulates the autophagy genes in wild-type N2, evident by increased GFP-tagged LGG-1 foci. However, hesperidin failed to upregulate the autophagy genes level in acr-16 mutant worms that suggests autophagy activation is mediated through acr-16. In addition, hesperidin showed antiaging and anti-oxidative effects, as evidenced by positive changes in different markers necessary for health span and lifespan. Additionally, hesperidin could upregulate acr-16 and autophagy genes (lgg-1 & bec-1) and ameliorates Aβ-induced toxicity as observed with reduce ROS accumulation, paralysis rate, and enhanced lifespan even in worms AD model CL4176 and CL2006 strain. Our finding suggests that hesperidin significantly enhances oxidative stress resistance, prolongs the lifespan, and protects against Aβ-induced toxicity in C. elegans. acr-16 mediated autophagy and antioxidation is associated with anti-aging and anti-Aβ effect of hesperidin.
    Keywords:  Alzheimer's disease; Autophagy; C. elegans; Hesperidin; Oxidative stress; acr-16
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2023.10.408
  5. Small. 2023 Oct 29. e2302907
    A Multisystemic Approach Revealed Aminated Polystyrene Nanoparticles-Induced Neurotoxicity.
    Laura Schröter, Lena Jentsch, Silvia Maglioni, Amanda Muñoz-Juan, Tina Wahle, Annette Limke, Anna von Mikecz, Anna Laromaine, Natascia Ventura.
      Exposure to plastic nanoparticles has dramatically increased in the last 50 years, and there is evidence that plastic nanoparticles can be absorbed by organisms and cross the blood-brain-barrier (BBB). However, their toxic effects, especially on the nervous system, have not yet been extensively investigated, and most of the knowledge is based on studies using different conditions and systems, thus hard to compare. In this work, physicochemical properties of non-modified polystyrene (PS) and amine-functionalized PS (PS-NH2 ) nanoparticles are initially characterized. Advantage of a multisystemic approach is then taken to compare plastic nanoparticles effects in vitro, through cytotoxic readouts in mammalian cell culture, and in vivo, through behavioral readouts in the nematode Caenorhabditis elegans (C. elegans), a powerful 3R-complying model organism for toxicology studies. In vitro experiments in neuroblastoma cells indicate a specific cytotoxic effect of PS-NH2 particles, including a decreased neuronal differentiation and an increased Amyloid β (Aβ) secretion, a sensitive readout correlating with Alzheimer's disease pathology. In parallel, only in vivo treatments with PS-NH2 particles affect C. elegans development, decrease lifespan, and reveal higher sensitivity of animals expressing human Aβ compared to wild-type animals. In summary, the multisystemic approach discloses a neurotoxic effect induced by aminated polystyrene nanoparticles.
    Keywords:  Alzheimer's disease; C. elegans; environment; model organisms; nanoplastic particles; neurotoxicity
    DOI:  https://doi.org/10.1002/smll.202302907
  6. Sci Total Environ. 2023 Oct 31. pii: S0048-9697(23)06838-9. [Epub ahead of print] 168211
    Crucial physicochemical factors mediating mitochondrial toxicity of nanoparticles at noncytotoxic concentration.
    Ze Zhang, Gan Miao, Lin Lu, Hao Yin, Yingzhu Wang, Baoqiang Wang, Ruonan Pan, Chuer Zheng, Xiaoting Jin.
      Nanomaterials have been extensively applied in multiple industries, among which silver nanoparticles (AgNPs), silicon dioxide nanoparticles (SiNPs), and gold nanoparticles (AuNPs) have become representative of widely consumed NPs. Limited knowledge is available regarding the subcellular responses of NPs with different physicochemical properties, i.e. material type and size, under the noncytotoxic concentrations. Macrophages are important sensitive cells exposed to NPs, and mitochondria are sensitive organelles that respond at the subcellular level. Herein, we found that sublethal concentrations of AgNPs and SiNPs, not AuNPs, decreased the mitochondrial membrane potential (MMP) and tubular mitochondria, and further resulted in an increase of ROS level and a decrease of ATP generation. AgNPs and SiNPs can also disturb mitochondrial dynamics manifested as increasing Mfn2 expression and decreasing Drp1 expression. Further assessments for mitochondrial function showed that AgNPs and SiNPs exposure led to a decrease in the gene expressions related to complex I (Ndufa8 and Ndufs2), complex III (Uqcrc2 and Uqcrfs1), complex IV (Cox6b1), and activity of complex I, suggesting their potential roles in impairing cellular respiration. In terms of the effects of NPs with different sizes, stronger toxicity was observed in smaller-sized nanoparticles. Among the above mitochondrial changes, we identified that ROS, ATP, MMP, tubular mitochondria, and expression of Drp1 were relatively sensitive indicators in subcellular response to NPs. With the above sensitive indicators, the comparison of heterogeneity between material type and size of the NPs showed that material type occupied a main influence on subcellular mitochondrial effects. Our finding provided important data on the potential subcellular risks of NPs, and indicated the vital role of material type for a better understanding of the nanomaterial biological safety.
    Keywords:  Material type; NPs; Noncytotoxic concentration; Sensitive mitochondrial response; Size
    DOI:  https://doi.org/10.1016/j.scitotenv.2023.168211
  7. Curr Neuropharmacol. 2023 Oct 17.
    Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond.
    Jenny Valentina Garmendia, Claudia Valentina De Sanctis, Viswanath Das, Narendran Annadurai, Marián Hajduch, Juan Bautista De Sanctis.
      Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, β amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.
    Keywords:  Alzheimer's disease (AD); Neurodegenerative diseases (NDs); Parkinson's disease (PD); Tau; autoimmunity; neurodegeneration; neuroinflammation; therapy; vaccines.; α-synuclein; β-amyloid
    DOI:  https://doi.org/10.2174/1570159X22666231017141636
  8. Sci Adv. 2023 11 03. 9(44): eadh2584
    UNC-49 is a redox-sensitive GABAA receptor that regulates the mitochondrial unfolded protein response cell nonautonomously.
    Franziska Pohl, Allison L Germann, Jack Mao, Sydney Hou, Bayode Bakare, Paul Kong Thoo Lin, Kyari Yates, Michael L Nonet, Gustav Akk, Kerry Kornfeld, Jason M Held.
      The γ-aminobutyric acid-mediated (GABAergic) system participates in many aspects of organismal physiology and disease, including proteostasis, neuronal dysfunction, and life-span extension. Many of these phenotypes are also regulated by reactive oxygen species (ROS), but the redox mechanisms linking the GABAergic system to these phenotypes are not well defined. Here, we report that GABAergic redox signaling cell nonautonomously activates many stress response pathways in Caenorhabditis elegans and enhances vulnerability to proteostasis disease in the absence of oxidative stress. Cell nonautonomous redox activation of the mitochondrial unfolded protein response (mitoUPR) proteostasis network requires UNC-49, a GABAA receptor that we show is activated by hydrogen peroxide. MitoUPR induction by a spinocerebellar ataxia type 3 (SCA3) C. elegans neurodegenerative disease model was similarly dependent on UNC-49 in C. elegans. These results demonstrate a multi-tissue paradigm for redox signaling in the GABAergic system that is transduced via a GABAA receptor to function in cell nonautonomous regulation of health, proteostasis, and disease.
    DOI:  https://doi.org/10.1126/sciadv.adh2584
  9. Neural Regen Res. 2024 Jun 01. 19(6): 1197-1198
    Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson's disease.
    Davide Cossu, Nobutaka Hattori.
      
    DOI:  https://doi.org/10.4103/1673-5374.385873
  10. Biomed Pharmacother. 2023 Oct 30. pii: S0753-3322(23)01586-X. [Epub ahead of print]168 115788
    Flavonoids: Their putative neurologic roles, epigenetic changes, and gut microbiota alterations in Parkinson's disease.
    Yasemin Açar, Duygu Ağagündüz, Paola De Cicco, Raffaele Capasso.
      Parkinson's Disease (PD), a neurodegenerative disorder, is characterized by the degeneration of progressive dopaminergic (DA) neurons in the substantia nigra region of the human midbrain. Although just what causes PD remains a mystery, it is known that oxidative stress (OS) as well as mitochondrial dysfunction, neuro-inflammation, and insufficient neurotrophic support play a role in the disease's pathophysiology. Phytochemicals are a diverse small molecule group derived from plants that can be classified into numerous classes on the basis of their biological activities and chemical structure. Of these groups of phytochemicals, the most abundant, which has well-established anti-Parkinson's effects, are polyphenols. Flavonoids, including naringin and naringenin, genistein, kaempferol, anthocyanins, epigallocatechin-3-gallate, and baicalein are plant-based biologically active polyphenols, which have been shown to exhibit therapeutic potential when used as treatment for a variety of pathological illnesses, such as neurodegenerative diseases (NDs) and PD. Recently, it was reported that flavonoids have beneficial effects on PD, such as the protection of DA neurons, improvement of motor and cognitive abilities, regulation of signaling pathways, and modulation of OS and neuro-inflammation. In addition, by changing the composition of bacteria in gut microbiota, flavonoids reduce pathogenic strains and promote the growth of beneficial strains. In this context, the current paper will provide a literature review on the neurological roles that flavonoids play, as one of the most abundant phytochemical families, in PD.
    Keywords:  Flavonoids; Neurodegenerative diseases; Parkinson’s disease; Polyphenols
    DOI:  https://doi.org/10.1016/j.biopha.2023.115788
  11. BMB Rep. 2023 Nov 02. pii: 6058. [Epub ahead of print]
    Coordination chemistry of mitochondrial copper metalloenzymes: exploring implications for copper dyshomeostasis in cell death.
    Daeun Shim, Jiyeon Han.
      Mitochondria, fundamental cellular organelles that govern energy metabolism, hold a pivotal role in cellular vitality. While consuming dioxygen to produce adenosine triphosphate (ATP), the electron transfer process within mitochondria can engender the formation of reactive oxygen species that exert dual roles in endothelial homeostatic signaling and oxidative stress. In the context of the intricate electron transfer process, several metal ions that include copper, iron, zinc, and manganese serve as crucial cofactors in mitochondrial metalloenzymes to mediate the synthesis of ATP and antioxidant defense. In this mini review, we provide a comprehensive understanding of the coordination chemistry of mitochondrial cuproenzymes. In detail, superoxide dismutase 1 (SOD1) functions in detoxifying superoxide into hydrogen peroxide, while cytochrome c oxidase (CcO) reduces dioxygen to water coupled with proton pumping to generate an electrochemical gradient. With an emphasis on the catalytic reactions of the copper metalloenzymes and insights into their ligand environment, we also outline the metalation process of these enzymes throughout the copper trafficking system. The impairment of copper homeostasis can trigger mitochondrial dysfunction, and potentially lead to the development of copper-related disorders. We describe the current knowledge regarding copper-mediated toxicity mechanisms, thereby shedding light on prospective therapeutic strategies for pathologies intertwined with copper dyshomeostasis.
  12. Front Biosci (Landmark Ed). 2023 Oct 20. 28(10): 255
    Secondary Protein Aggregates in Neurodegenerative Diseases: Almost the Rule Rather than the Exception.
    Fabio Moda, Arianna Ciullini, Ilaria Linda Dellarole, Annalisa Lombardo, Nicole Campanella, Giuseppe Bufano, Federico Angelo Cazzaniga, Giorgio Giaccone.
      The presence of protein aggregates is a hallmark of many neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Traditionally, each disease has been associated with the aggregation of specific proteins, which serve as disease-specific biomarkers. For example, aggregates of α-synuclein (α-syn) are found in α-synucleinopathies such as PD, dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Similarly, AD is characterized by aggregates of amyloid-beta (Aβ) and tau proteins. However, it has been observed that these protein aggregates can also occur in other neurodegenerative diseases, contributing to disease progression. For instance, α-syn aggregates have been detected in AD, Down syndrome, Huntington's disease, prion diseases, and various forms of FTLD. Similarly, Aβ aggregates have been found in conditions like DLB and PD. Tau aggregates, in addition to being present in primary tauopathies, have been identified in prion diseases, α-synucleinopathies, and cognitively healthy aged subjects. Finally, aggregates of TDP-43, typically associated with FTLD and amyotrophic lateral sclerosis (ALS), have been observed in AD, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), MSA, DLB, and other neurodegenerative diseases. These findings highlight the complexity of protein aggregation in neurodegeneration and suggest potential interactions and common mechanisms underlying different diseases. A deeper understating of this complex scenario may eventually lead to the identification of a better elucidation of the pathogenetic mechanisms of these devastating conditions and hopefully new therapeutic stragegies.
    Keywords:  TDP-43 proteinopathies; alpha-synucleinopathies; biomarker; neurodegeneration; neuropathology; protein aggregation; tautopathies
    DOI:  https://doi.org/10.31083/j.fbl2810255
This page is being maintained by Thomas Krichel. It was last updated on 2024‒11‒22 at 4:21.