bims-metalz 2023-12-03 papers

bims-metalz

Biomed News

on Metabolic causes of Alzheimer’s disease

Issue of 2023–12–03
eight papers selected by
Mikaila Chetty, Goa University

Nanophytomedicines as Therapeutic Agents for Parkinson's Disease.
A Recent Update on Pathophysiology and Therapeutic Interventions of Alzheimer's Disease.
Decoding metabolic signatures in Alzheimer's disease: a mitochondrial perspective.
The Role of Gut Microbiota in Neurodegenerative Diseases: Current Insights and Therapeutic Implications.
Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.
Simira cordifolia protects against metal induced-toxicity in Caenorhabditis elegans.
Lippia origanoides essential oil increases longevity and ameliorates β-amyloid peptide-induced toxicity in Caenorhabditis elegans.
Omega-3 PUFA and the fitness and cognition of the nematode Caenorhabditis elegans under different environmental conditions.

ACS Omega. 2023 Nov 14. 8(45): 42045-42061

Nanophytomedicines as Therapeutic Agents for Parkinson's Disease.

Jessica Burns, Amy Claire Buck, Sarah D' Souza, Admire Dube, Soraya Bardien.

Phytochemicals are promising therapeutics for various neurodegenerative disorders, including Parkinson's disease (PD). However, their efficacy, pharmacokinetic properties, and penetration across the blood-brain barrier can be improved using delivery systems such as nanoparticles. We reviewed recently published work in which nanoparticles were used to deliver phytochemicals toward PD treatment. The studies show that nanoparticles not only improve the pharmacological effect of the phytochemicals but also enable targeting to the brain and crossing of the blood-brain barrier. Various ligands were added to the nanoparticles to improve blood-brain barrier transportation. The promising findings from the published studies reveal that more research into nanophytomedicine approaches as therapeutic targets for PD is warranted, especially since they have the potential to protect against key features of PD, including α-synuclein aggregation, mitochondrial dysfunction, and dopaminergic neuronal death. Furthermore, future directions should involve smart designs to tailor nanoparticles for improved therapeutic delivery by modifying their features, such as architecture, surface and material properties, targeting ligands, and responsiveness.

DOI: https://doi.org/10.1021/acsomega.3c04862
Curr Pharm Des. 2023 Nov 30.

A Recent Update on Pathophysiology and Therapeutic Interventions of Alzheimer's Disease.

Mohd Kashif, Prathibha Sivaprakasam, Poornima Vijendra, Mohammad Waseem, Ashok Kumar Pandurangan.

   AIM: Alzheimer's disease (AD) has been identified as a progressive brain disorder associated with memory dysfunction and the accumulation of β-amyloid plaques and neurofibrillary tangles of τ protein. Mitochondria is crucial in maintaining cell survival, cell death, calcium regulation, and ATP synthesis. Mitochondrial dysfunction and linked calcium overload have been involved in the pathogenesis of AD. CRM2 (Collapsin response mediator protein-2) is involved in endosomal lysosomal trafficking as well as autophagy, and their reduced level is also a primary culprit in the progression of AD. In addition, Cholinergic neurotransmission and neuroinflammation are two other mechanisms implicated in AD onset and might be protective targets to attenuate disease progression. The microbiota-gut-brain axis (MGBA) is another crucial target for AD treatment. Crosstalk between gut microbiota and brain mutually benefitted each other, dysbiosis in gut microbiota affects the brain functions and leads to AD progression with increased AD-causing biomarkers. Despite the complexity of AD, treatment is only limited to symptomatic management. Therefore, there is an urgent demand for novel therapeutics that target associated pathways responsible for AD pathology. This review explores the role of different mechanisms involved in AD and possible therapeutic targets to protect against disease progression.
BACKGROUND: Amidst various age-related diseases, AD is the most deleterious neurodegenerative disorder that affects more than 24 million people globally. Every year, approximately 7.7 million new cases of dementia have been reported. However, to date, no novel disease-modifying therapies are available to treat AD.
OBJECTIVE: The aim of writing this review is to highlight the role of key biomarker proteins and possible therapeutic interventions that could play a crucial role in mitigating the ongoing prognosis of Alzheimer's disease.
MATERIALS AND METHODS: The available information about the disease was collected through multiple search engines, including PubMed, Science Direct, Clinical Trials, and Google Scholar.
RESULTS: Accumulated pieces of evidence reveal that extracellular aggregation of β-amyloid plaques and intracellular tangles of τ protein are peculiar features of perpetuated Alzheimer's disease (AD). Further, the significant role of mitochondria, calcium, and cholinergic pathways in the pathogenesis of AD makes the respiratory cell organelle a crucial therapeutic target in this neurodegenerative disease. All currently available drugs either delay the clinical damage to cells or temporarily attenuate some symptoms of Alzheimer's disease.
CONCLUSION: The pathological features of AD are extracellular deposition of β-amyloid, acetylcholinesterase deregulation, and intracellular tangles of τ protein. The multifactorial heterogeneity of disease demands more research work in this field to find new therapeutic biological targets.

Keywords:  ? protein; ?-amyloid; Alzheimer’s disease; Neurodegenerative disorders; acetylcholinesterase; dementia

DOI:  https://doi.org/10.2174/0113816128264355231121064704
Cell Death Discov. 2023 Dec 01. 9(1): 432

Decoding metabolic signatures in Alzheimer's disease: a mitochondrial perspective.

Daniele Bano, Dan Ehninger, Giacinto Bagetta.

Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative diseases and accounts for the majority of dementia cases worldwide. Tremendous ongoing efforts of basic and clinical research have expanded our knowledge on AD and its complex multifactorial pathogenesis. For sporadic AD, it is widely assumed that silent and early symptomatic stages initiate decades before the irreversible decline in cognitive abilities that ultimately lead to debilitating conditions. In addition to amyloid plaques and tau-containing neurofibrillary tangles as the most prominent hallmarks of AD lesions within the affected brain areas, we now possess a broader collection of pathological signatures that are associated with AD development and progression. In this regard, there is a substantial body of evidence suggesting that hypometabolism occurs in the brains of individuals at the prodromal stage before dementia is diagnosed, which may reflect an early role of metabolic dysfunction in AD. This perspective surveys the vast literature and critically assesses the current evidence demonstrating a mitochondrial contribution to AD. Additionally, we discuss our interpretations of the reported mitochondrial signatures and consider how altered mitochondrial bioenergetics may be an additional risk factor for AD pathogenesis.

DOI: https://doi.org/10.1038/s41420-023-01732-3
Cureus. 2023 Oct;15(10): e47861

The Role of Gut Microbiota in Neurodegenerative Diseases: Current Insights and Therapeutic Implications.

Arpit Jain, Suryansh Madkan, Praful Patil.

  Small microscopic entities known as microbes, having a population of hundreds of billions or perhaps even in trillions, reside in our gastrointestinal tract. A healthy immune system, digestion, and creation of vitamins and enzymes are all thanks to these microbes. However, new research has shown a hitherto unrecognized connection between the microbiota of the intestines and the genesis of neurodegenerative diseases. Neurons in the CNS gradually deteriorate in neurodegenerative illnesses like multiple sclerosis and Parkinson's disease (PD). This deterioration impairs cognitive and physical function. Amyotrophic lateral sclerosis (ALS), PD, and Alzheimer's disease (AD) are just a few examples of neurodegenerative illnesses that pose a serious threat to world health and have few effective treatments. Recent research suggests that the gut microbiota, a diverse microbial population found in the gastrointestinal system, may substantially impact the cause and development of various diseases. The discovery of altered gut microbiota composition in people with these illnesses is one of the most critical lines of evidence connecting gut microbiota dysbiosis to neurodegenerative diseases. AD patients have a distinct characteristic of having a particular microbiota profile. In addition, an excess population of a specific microbe data profile is seen as compared to a healthy individual. Similar changes in the gut microbiota composition have been noted in people with multiple sclerosis and PD. The latest study indicates the potential that dysbiosis, a condition characterized by alteration in the intestinal microbiota's makeup and functioning, may have an effect on the onset and progression of neurodegenerative diseases, including PD and multiple sclerosis. In order to emphasize any potential underlying mechanisms and examine potential treatment repercussions, the review article's goal is to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders. The review article aims to summarize current knowledge about the connection between gut microbiota and neurodegenerative disorders, highlighting potential underlying mechanisms and examining potential treatment repercussions.

Keywords:  alzheimer's disease; amytrophic lateral sclerosis; dysbiosis; gut microbiota; parkinson' s disease

DOI:  https://doi.org/10.7759/cureus.47861
CNS Neurol Disord Drug Targets. 2023 Nov 28.

Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.

Kadja Luana Chagas Monteiro, Thiago Mendonça de Aquino, Edeildo Ferreira da Silva-Júnior.

  Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products. These studies focus on inhibiting the formation of amyloid plaques and tau protein tangles, with the objective of potentially alleviating or delaying AD.

Keywords:  Alzheimer’s disease; Flavonoids; Neurodegeneration; Polyphenols

DOI:  https://doi.org/10.2174/0118715273273539231114095300
Front Pharmacol. 2023 ;14 1235190

Simira cordifolia protects against metal induced-toxicity in Caenorhabditis elegans.

Margareth Duran-Izquierdo, Lucellys Sierra-Marquez, Maria Taboada-Alquerque, Jesus Olivero-Verbel.

  Simira cordifolia (Hook.f.) Steyerm (Rubiaceae) is a vascular plant used in Northern Colombia as a source of pigments and wood. However, there is a lack of information regarding its pharmacology and toxicity. This research aimed to study the hydroalcoholic extract of Simira cordifolia as a protector against metal-induced toxicity in Caenorhabditis elegans. Preliminary phytochemical screening of the hydroalcoholic extract of S. cordifolia (HAE-Sc) was conducted using HPLC-ESI-QTOF. Wild-type N2 C. elegans larvae were exposed to different concentrations of HAE-Sc evaluating lethality (50-5000 μg/mL), growth, lifespan, resistance to heat stress, and its protective effect against Mercury (Hg)-, Lead (Pb)- and Cadmium (Cd)-induced lethality (50-1000 μg/mL). The main metabolites present in the extract were iridoids, β-carboline-alkaloids and polyphenols. Bioassays demonstrated that HAE-Sc exhibited low toxicity, with significant lethality (4.2% and 9.4%) occurring at 2500-5000 μg/mL. Growth inhibition reached up to 23.3%, while reproduction declined 13% and 17% at concentrations 500 and 1000 μg/mL, respectively. HAE-Sc enhanced the survival rate of the nematode under thermal stress by up to 79.8%, and extended the mean lifespan of worms by over 33% compared to control. The average lifespan was prolonged by 15.3% and 18.5% at 50 and 100 μg/mL HAE-Sc, respectively. The extract (1000 μg/mL) was able to reduce the death of C. elegans in the presence of heavy metals up to 65.9, 96.8% and 87% for Pb, Hg, and Cd, respectively. In summary, S. cordifolia shows potential protective effects in C. elegans against toxicity caused by heavy metals and heat.

Keywords:  alkaloids; biodiversity; cadmium; lead; mercury; natural products

DOI:  https://doi.org/10.3389/fphar.2023.1235190
Nat Prod Res. 2023 Dec 02. 1-9

Lippia origanoides essential oil increases longevity and ameliorates β-amyloid peptide-induced toxicity in Caenorhabditis elegans.

Ana Maria Henrique Moniz, Francisco Humberto Xavier Junior, Giovanna Melo Martins Silva, Ana Cristina Gonçalves Reis de Melo, Maylla Maria Correia Leite Silva, Weslley Souza Paiva, Hugo Alexandre Oliveira Rocha, Luiz Antônio Mendonça Alves da Costa, Antônio Alves de Melo Filho, Riva de Paula Oliveira.

  Lippia origanoides essential oil (LOEO) is extensively utilised as food preservative due to its antioxidant and antibacterial activities. In this study, the antioxidant and anti-ageing effects of LOEO was investigated in vivo using the nematode Caenorhabditis elegans. The gas chromatography-mass spectrometry analysis indicated that the main components of LOEO are carvacrol and thymol. LOEO treatment improved physiological parameters such as pharyngeal pumping, locomotion and body size indicating that is not toxic to C. elegans. LOEO treatment showed antioxidant effect in C. elegans by reducing endogenous ROS (Reactive Oxygen Species) production and increasing their survival under oxidative stress. Finally, LOEO treatment significantly extended C. elegans lifespan and alleviated the paralysis induced by β-amyloid peptide overexpression in the muscle. This work demonstrates for the first time LOEO antioxidant and anti-ageing properties on an organism level providing a valuable proof of principle to support further studies in the development of nutraceuticals or antioxidant phytotherapy.

Keywords:  Alzheimer disease; Antibacterial; anti-ageing; antioxidant; carvacrol; thymol

DOI:  https://doi.org/10.1080/14786419.2023.2287183
Comp Biochem Physiol B Biochem Mol Biol. 2023 Nov 29. pii: S1096-4959(23)00100-8. [Epub ahead of print] 110925

Omega-3 PUFA and the fitness and cognition of the nematode Caenorhabditis elegans under different environmental conditions.

Ralph Menzel, Xuchao Zhang, Tamara Pietrucik, Antonia Bathelt, Liliane Ruess.

  Many invertebrate species possess the metabolic ability to synthesize long-chain ω3 polyunsaturated fatty acids (PUFA) de novo. Due to their diverse effects on membrane architecture, neuroplasticity, growth and reproduction, PUFA have a high potential to positively influence the fitness of an organism. But how and when do these supposed advantages actually come into play? Other species, that are often closely related, pass natural selection without this special metabolic ability. The ω3-PUFA rich model organism Caenorhabditis elegans (Nematoda) and its mutant fat-1(wa9), lacking these PUFA, are a suitable test system. We analyzed potential impairments in reproduction and growth in a soil assay. Further, chemotaxis after aversive olfactory, associative learning and integration of a second sensory signal were assessed on agar plates. Moreover, we analyzed the phospholipid pattern of both C. elegans strains and further free-living nematodes species at different temperatures. While the phenotypic effects were rather small under standard conditions, lowering the temperature to 15 or even 10 °C or reducing the soil moisture, led to significant limitations, with the investigated parameters for neuroplasticity being most impaired. The ω3-PUFA free C. elegans mutant strain fat-1 did not adapt the fatty acid composition of its phospholipids to a decreasing temperature, while ω3-PUFA containing nematodes proportionally increased this PUFA group. In contrats, other ω3-PUFA free nematode species produced significantly more ω6-PUFA. Thus, the ability to synthesize long-chain ω3-PUFA de novo likely is fundamental for an increase in neuroplasticity and an efficient way for regulating membrane fluidity to maintain their functionality.

Keywords:  Caenorhabditis elegans; Chemotaxis; Learning; Omega-3 PUFA; PLFA

DOI:  https://doi.org/10.1016/j.cbpb.2023.110925