bims-metalz 2023-09-03 papers

bims-metalz

Biomed News

on Metabolic causes of Alzheimer’s disease

Issue of 2023–09–03
eight papers selected by
Mikaila Chetty, Goa University

Editorial: Reviews in the impact of gut microbiota in health and disease.
Peripheral metabolic alterations associated with pathological manifestations of Parkinson's disease in gut-brain axis-based mouse model.
Inflammasome assembly in neurodegenerative diseases.
Insights on Quercetin Therapeutic Potential for Neurodegenerative Diseases and its Nano-technological Perspectives.
In-vivo screening implicates endoribonuclease Regnase-1 in modulating senescence-associated lysosomal changes.
Break and accelerator-The mechanics of Tau (and amyloid) toxicity.
Antioxidant Peptides Derived from Millet Bran Promote Longevity and Stress Resistance in Caenorhabditis elegans.
Cooperation between neurovascular dysfunction and Aβ in Alzheimer's disease.

Front Microbiol. 2023 ;14 1230925

Editorial: Reviews in the impact of gut microbiota in health and disease.

Junling Shi.



Keywords:  gut microbiome; human health and disease; pathogen; reviews; therapy

DOI:  https://doi.org/10.3389/fmicb.2023.1230925
Front Mol Neurosci. 2023 ;16 1201073

Peripheral metabolic alterations associated with pathological manifestations of Parkinson's disease in gut-brain axis-based mouse model.

Eugene Huh, Jin Gyu Choi, Mee Youn Lee, Jin Hee Kim, Yujin Choi, In Gyoung Ju, Hyeyoon Eo, Myoung Gyu Park, Dong-Hyun Kim, Hi-Joon Park, Choong Hwan Lee, Myung Sook Oh.

   Introduction: Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis (P. mirabilis)-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis.
Methods: We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis-induced disease progression and pathology.
Results and discussion: Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis-induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis-mediated pathology of brain neurodegeneration.

Keywords:  Parkinson’s disease; Proteus mirabilis; endogenous metabolites; glycation; microbiota-gut-brain axis

DOI:  https://doi.org/10.3389/fnmol.2023.1201073
Trends Neurosci. 2023 Aug 24. pii: S0166-2236(23)00174-1. [Epub ahead of print]

Inflammasome assembly in neurodegenerative diseases.

Jagjit Singh, Maria L Habean, Nikhil Panicker.

  Neurodegenerative disorders are characterized by the progressive dysfunction and death of selectively vulnerable neuronal populations, often associated with the accumulation of aggregated host proteins. Sustained brain inflammation and hyperactivation of inflammasome complexes have been increasingly demonstrated to contribute to neurodegenerative disease progression. Here, we review molecular mechanisms leading to inflammasome assembly in neurodegeneration. We focus primarily on four degenerative brain disorders in which inflammasome hyperactivation has been well documented: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We discuss shared and divergent principles of inflammasome assembly across these disorders, and underscore the differences between neurodegeneration-associated inflammasome activation pathways and their peripheral-immune counterparts. We examine how aberrant assembly of inflammasome complexes may amplify pathology in neurodegeneration, including misfolded protein aggregation, and highlight prospects for neurotherapeutic interventions based on targeting inflammasome pathways.

Keywords:  AIM2; Alzheimer’s disease; NLRC4; NLRP1; NLRP3; Parkinson’s disease; amyotrophic lateral sclerosis; frontotemporal dementia; multiple sclerosis

DOI:  https://doi.org/10.1016/j.tins.2023.07.009
Curr Pharm Biotechnol. 2023 Aug 30.

Insights on Quercetin Therapeutic Potential for Neurodegenerative Diseases and its Nano-technological Perspectives.

Rajat Goyal, Garima Mittal, Suman Khurana, Neelam Malik, Vivek Kumar, Arti Soni, Hitesh Chopra, Mohammad Amjad Kamal.

  The neurodegeneration process begins in conjunction with the aging of the neurons. It manifests in different parts of the brain as Aβ plaques, neurofibrillary tangles, Lewy bodies, Pick bodies, and other structures, which leads to progressive loss or death of neurons. Quercetin (QC) is a flavonoid compound found in fruits, tea, and other edible plants have antioxidant effects that have been studied from subcellular compartments to tissue levels in the brain. Also, quercetin has been reported to possess a neuroprotective role by decreasing oxidative stress-induced neuronal cell damage.The use of QC for neurodegenerative therapy, the existence of the blood-brain barrier (BBB) remains a significant barrier to improving the clinical effectiveness of the drug, so finding an innovative solution to develop simultaneous BBB-crossing ability of drugs for treating neurodegenerative disorders and improving neurological outcomes is crucial. The nanoparticle formulation of QC is considered beneficial and useful for its delivery through this route for the treatment of neurodegenerative diseases seems necessary. Increased QC accumulation in the brain tissue and more significant improvements in tissue and cellular levels are among the benefits of QC-involved nanostructures.

Keywords:  Quercetin; antioxidant; blood-brain barrier; nanoparticles; nanotechnology; neurodegenerative disorders

DOI:  https://doi.org/10.2174/1389201025666230830125410
Geroscience. 2023 Aug 29.

In-vivo screening implicates endoribonuclease Regnase-1 in modulating senescence-associated lysosomal changes.

Richard Venz, Anita Goyala, Abel Soto-Gamez, Tugce Yenice, Marco Demaria, Collin Y Ewald.

  Accumulation of senescent cells accelerates aging and age-related diseases, whereas preventing this accumulation extends the lifespan in mice. A characteristic of senescent cells is increased staining with β-galactosidase (β-gal) ex vivo. Here, we describe a progressive accumulation of β-gal staining in the model organism C. elegans during aging. We show that distinct pharmacological and genetic interventions targeting the mitochondria and the mTORC1 to the nuclear core complex axis, the non-canonical apoptotic, and lysosomal-autophagy pathways slow the age-dependent accumulation of β-gal. We identify a novel gene, rege-1/Regnase-1/ZC3H12A/MCPIP1, modulating β-gal staining via the transcription factor ets-4/SPDEF. We demonstrate that knocking down Regnase-1 in human cell culture prevents senescence-associated β-gal accumulation. Our data provide a screening pipeline to identify genes and drugs modulating senescence-associated lysosomal phenotypes.

Keywords:  Beta-gal; Longevity; Metformin; Senescence; Senolytic

DOI:  https://doi.org/10.1007/s11357-023-00909-z
Cytoskeleton (Hoboken). 2023 Aug 26.

Break and accelerator-The mechanics of Tau (and amyloid) toxicity.

Esteban Cruz, Rebecca M Nisbet, Jürgen Götz.

  Aggregates of the microtubule-associated protein Tau define more than a dozen primary tauopathies, and together with amyloid-β, the secondary tauopathy Alzheimer's disease (AD). Historically, Tau has been viewed as executor of amyloid-β toxicity, with the two molecules working together as "trigger and bullet." Given the two protein's opposing roles in protein translation, we wish to introduce another metaphor, borrowing from the mechanics of a car, with amyloid-β boosting Tau translation, whereas Tau puts a break on global translation. The underlying studies entail an alternative hypothesis regarding Tau's subcellular accumulation in AD, namely its de novo synthesis in the somatodendritic domain rather than the relocalization from the axon upon dissociation from microtubules. We contest that it may be worth (given Tau's 50th birthday) to revisit some entrenched dogmas about Tau's pathophysiology.

Keywords:  Alzheimer's disease; Frontotemporal dementia; amyloid; protein translation; tau

DOI:  https://doi.org/10.1002/cm.21781
Plant Foods Hum Nutr. 2023 Sep 01.

Antioxidant Peptides Derived from Millet Bran Promote Longevity and Stress Resistance in Caenorhabditis elegans.

Chen Li, Wenjing Xu, Xiangyu Zhang, Xiaodong Cui, Apollinaire Tsopmo, Jiao Li.

  Millet bran as a by-product of millet grain processing remains a reservoir of active substances. In this study, functional millet bran peptides (MBPE) were obtained from bran proteins after alcalase hydrolysis and ultrafiltration. The activity of MBPE was assessed in vitro and in the model organism Caenorhabditis elegans (C. elegans). In vitro, compared to unhydrolyzed proteins, MBPE significantly enhanced the 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate (ABTS) and hydroxyl radicals scavenging activity, and the scavenging rate of MBPE with 15,000 U/g alcalase reached 42.79 ± 0.31%, 61.38 ± 0.41 and 45.69 ± 0.84%, respectively. In C. elegans, MBPE at 12.5 µg/mL significantly prolonged the lifespan by reducing lipid oxidation, oxidative stress, and lipofuscin levels. Furthermore, MBPE increased the activities of the antioxidant enzymes. Genetic analyses showed that MBPE-mediated longevity was due to a significant increase in the expression of daf-16 and skn-1, which are also involved in xenobiotic and oxidative stress responses. In conclusion, this study found that MBPE had antioxidant and life-prolonging effects, which are important for the development and utilization of millet bran proteins as resources of active ingredients.

Keywords:  Antioxidant activity; Caenorhabditis elegans; Life-prolonging effect; Millet bran peptides

DOI:  https://doi.org/10.1007/s11130-023-01100-7
Front Mol Neurosci. 2023 ;16 1227493

Cooperation between neurovascular dysfunction and Aβ in Alzheimer's disease.

Niya Wang, Xiang Yang, Zhong Zhao, Da Liu, Xiaoyan Wang, Hao Tang, Chuyu Zhong, Xinzhang Chen, Wenli Chen, Qiang Meng.

  The amyloid-β (Aβ) hypothesis was once believed to represent the pathogenic process of Alzheimer's disease (AD). However, with the failure of clinical drug development and the increasing understanding of the disease, the Aβ hypothesis has been challenged. Numerous recent investigations have demonstrated that the vascular system plays a significant role in the course of AD, with vascular damage occurring prior to the deposition of Aβ and neurofibrillary tangles (NFTs). The question of how Aβ relates to neurovascular function and which is the trigger for AD has recently come into sharp focus. In this review, we outline the various vascular dysfunctions associated with AD, including changes in vascular hemodynamics, vascular cell function, vascular coverage, and blood-brain barrier (BBB) permeability. We reviewed the most recent findings about the complicated Aβ-neurovascular unit (NVU) interaction and highlighted its vital importance to understanding disease pathophysiology. Vascular defects may lead to Aβ deposition, neurotoxicity, glial cell activation, and metabolic dysfunction; In contrast, Aβ and oxidative stress can aggravate vascular damage, forming a vicious cycle loop.

Keywords:  Alzheimer’s disease; blood–brain barrier; cerebral blood flow; neurovascular unit; β-Amyloid

DOI:  https://doi.org/10.3389/fnmol.2023.1227493