Current Advances in Mitochondrial Targeted Interventions in Alzheimer’s Disease DOI Creative Commons
Tiago Siqueira de Sousa, Paula I. Moreira, Susana Cardoso

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2331 - 2331

Published: Aug. 22, 2023

Alzheimer’s disease is the most prevalent neurodegenerative disorder and affects lives not only of those who are diagnosed but also their caregivers. Despite enormous social, economic political burden, AD remains a without an effective treatment with several failed attempts to modify course. The fact that clinical diagnosis often performed at stage which underlying pathological events in advanced conceivably irremediable state strongly hampers attempts. This raises awareness need identify characterize early brain changes AD, order possible novel therapeutic targets circumvent AD’s cascade events. One auspicious mitochondria, powerful organelles found nearly all cells body. A vast body literature has shown mitochondria from patients model organisms differ non-AD counterparts. In view this evidence, preserving and/or restoring mitochondria’s health function can represent primary means achieve advances tackle AD. review, we will briefly assess summarize previous latest evidence dysfunction particular focus be given recent updates strategy options aimed target faulty

Language: Английский

Roles of Oxidative Stress in Synaptic Dysfunction and Neuronal Cell Death in Alzheimer’s Disease DOI Creative Commons
Germán Plascencia‐Villa, George Perry

Antioxidants, Journal Year: 2023, Volume and Issue: 12(8), P. 1628 - 1628

Published: Aug. 17, 2023

Alzheimer’s disease (AD) is a brain disorder that progressively undermines memory and thinking skills by affecting the hippocampus entorhinal cortex. The main histopathological hallmarks of AD are presence abnormal protein aggregates (Aβ tau), synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, neuronal cell death. However, oxidative stress or damage also evident commonly overlooked considered consequence advancement dementia symptoms. control onset linked to activity amyloid-β peptide, which may serve as both antioxidant pro-oxidant molecules. Furthermore, correlated with proteins, nucleic acids, lipids in vulnerable populations, ultimately lead death through different molecular mechanisms. By recognizing an integral feature AD, alternative therapeutic preventive interventions developed tested potential complementary therapies for this devastating neurodegenerative disease.

Language: Английский

Citations

57
Mitochondrial dysfunction and neurological disorders: A narrative review and treatment overview DOI
Eman E. Alshial,

Muhammad Idris Abdulghaney,

Al-Hassan Soliman Wadan

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 334, P. 122257 - 122257

Published: Nov. 8, 2023

Language: Английский

Citations

44
What is really known about the effects of nicotinamide riboside supplementation in humans DOI Creative Commons
Mads V. Damgaard, Jonas T. Treebak

Science Advances, Journal Year: 2023, Volume and Issue: 9(29)

Published: July 21, 2023

Nicotinamide riboside is a precursor to the important cofactor nicotinamide adenine dinucleotide and has elicited metabolic benefits in multiple preclinical studies. In 2016, first clinical trial of was conducted test safety efficacy human supplementation. Many trials have since been aiming delineate health severe diseases humans. This review endeavors summarize critically assess 25 currently published research articles on supplementation identify any poorly founded claims assist field elucidating actual future potential for riboside. Collectively, oral displayed few clinically relevant effects, there an unfortunate tendency literature exaggerate importance robustness reported effects. Even so, may play role reduction inflammatory states shown some treatment diverse diseases.

Language: Английский

Citations

43
Gut microbiota-driven metabolic alterations reveal gut–brain communication in Alzheimer’s disease model mice DOI Creative Commons
Yijing Chen, Yinhu Li, Yingying Fan

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 23, 2024

The gut microbiota (GM) and its metabolites affect the host nervous system are involved in pathogeneses of various neurological diseases. However, specific GM alterations under pathogenetic pressure their contributions to "microbiota – metabolite brain axis" Alzheimer's disease (AD) remain unclear. Here, we investigated fecal, serum, cortical metabolomes APP/PS1 wild-type (WT) mice, revealing distinct hub bacteria AD mice within scale-free networks shared by both groups. Moreover, identified diverse peripheral central metabolic landscapes between WT that featured bile acids (e.g. deoxycholic isodeoxycholic acid) unsaturated fatty 11Z-eicosenoic palmitoleic acid). Machine-learning models revealed relationships differential/hub these signatures from periphery brain. Notably, AD-enriched Dubosiella affected occurrence via acid vice versa. Considering transgenic background propose enrichment impedes progression synthesis acid, which has protective properties against inflammation disorders. We another association involving fecal acid-mediated interactions Erysipelatoclostridium occurrence, was corroborated correlation deoxycholate levels cognitive scores humans. Overall, this study elucidated network alterations, landscapes, mediatory roles thus critical pathogenesis communications pressure.

Language: Английский

Citations

19
Glycine and aging: Evidence and mechanisms DOI Creative Commons
Adiv A. Johnson, Trinna Cuellar

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101922 - 101922

Published: March 31, 2023

The restriction of calories, branched-chain amino acids, and methionine have all been shown to extend lifespan in model organisms. Recently, glycine was found boost longevity genetically heterogenous mice. This simple acid similarly extends rats improves health mammalian models age-related disease. While compelling data indicate that is a pro-longevity molecule, divergent mechanisms may underlie its effects on aging. Glycine abundant collagen, building block for glutathione, precursor creatine, an acceptor the enzyme N-methyltransferase (GNMT). A review literature strongly implicates GNMT, which clears from body by taking methyl group S-adenosyl-L-methionine methylating form sarcosine. In flies, Gnmt required reduced insulin/insulin-like growth factor 1 signaling dietary fully lifespan. geroprotector spermidine requires upregulate autophagy genes longevity. Moreover, overexpression sufficient reduce levels. Sarcosine, or methylglycine, declines with age multiple species capable inducing both vitro vivo. Taken together, existing evidence suggests prolongs life mimicking activating autophagy.

Language: Английский

Citations

23
Genome-scale models in human metabologenomics DOI
Adil Mardinoğlu, Bernhard Ø. Palsson

Nature Reviews Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Language: Английский

Citations

10
Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study DOI Creative Commons
Hasan Türkez, Serkan Yıldırım, Elvan Şahin

et al.

Toxics, Journal Year: 2022, Volume and Issue: 10(8), P. 428 - 428

Published: July 28, 2022

Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure neurotoxic hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds used in a broad mix industries, from cosmetics pharmaceuticals agriculture. They affect critical biological functions cellular events enzymatic reactions, as well endocrinal mineral metabolisms. There limited dose-related data about boric acid (BA) other compounds, including colemanite (Col), ulexite (UX) borax (BX), which commercial prominence. In this study, we evaluate compounds' genetic, cytological, pathological against chloride (AlCl

Language: Английский

Citations

28
Peripheral Mitochondrial Dysfunction: A Potential Contributor to the Development of Metabolic Disorders and Alzheimer’s Disease DOI Creative Commons

Most Sultana,

Raksa Andalib Hia,

Oluwatosin Akinsiku

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(7), P. 1019 - 1019

Published: July 19, 2023

Alzheimer’s disease (AD) is a progressive neurodegenerative characterized by loss of function and eventual death neurons in the brain. Multiple studies have highlighted involvement mitochondria initiation advancement diseases. Mitochondria are essential for ATP generation, bioenergetics processes, regulation calcium homeostasis free radical scavenging. Disrupting any these processes has been acknowledged as major contributor to pathogenesis common diseases, especially AD. Several longitudinal demonstrated type 2 diabetes (T2D) risk factor origin dementia leading towards Even though emerging research indicates that anti-diabetic intervention promising option AD prevention therapy, results from clinical trials with agents not effective Interestingly, defective mitochondrial also reported contribute onset metabolic disorders including obesity T2D. The most prevalent consequences dysfunction include generation inflammatory molecules reactive oxygen species (ROS), which promote development impairment Current evidence an association impaired peripheral primary pathology; however, mechanisms still unknown. Therefore, this review, we discuss if dysfunction-mediated potential connection development, then would addressing better therapeutic outcomes preventing disorder-associated pathologies.

Language: Английский

Citations

16
A Review of Recent Advances in the Management of Alzheimer’s Disease DOI Open Access

Skylynn Thangwaritorn,

Christopher S. Lee,

Elena Metchikoff

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: April 16, 2024

Alzheimer's disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed attempted treatments, this remains major puzzle public health systems worldwide. The initial part article provides an overview illustration primary mechanisms responsible for neuronal damage AD. Subsequently, it offers critical evaluation noteworthy studies on pharmacological therapy AD outlines recent advancements novel approaches to managing condition. Main properties, categorization, Food Drug Administration (FDA) status, action, benefits, side effects classical recently treatments are described. conventional agents revised comprise cholinesterase inhibitors, monoclonal antibodies, other therapies, such as memantine, valproic acid, rosiglitazone. innovative reviewed antibodies: donanemab, gantenerumab, solanezumab, bapineuzumab, crenezumab, semorinemab. Nutritional supplements alpha-tocopherol (vitamin E) caprylidene also revised. Tau amyloid-targeting include methylthioninium moiety (MT), leuco-methylthioninium bis (LMTM), oxidized MT, tramiprosate, which inhibits beta-amyloid (Aβ) monomer aggregation into toxic oligomers. Antidiabetic anti-neuroinflammation drugs treatment discussed. antidiabetic NE3107, anti-inflammatory insulin sensitizer, diabetes mainstream drug metformin. anti-neuroinflammatory therapies use sodium oligomannate (GV-971), infusions with intravenous immunoglobulin aiming decrease plasma levels constituents Aβ plaques, masitinib, tyrosine kinase inhibitor that impacts mast microglia cells. Additional being currently tested phase-2 clinical trials, atomoxetine (selective norepinephrine reuptake inhibitor), losartan (angiotensin 2 receptor agonist), genistein (anti-inflammatory isoflavone neuroprotective agent), trans-resveratrol (polyphenol antioxidant plant estrogen), benfotiamine (synthetic thiamine precursor), were reviewed. Lastly, targeting Alzheimer's-associated symptoms, brexpiprazole (serotonin dopamine activity modulator) suvorexant (orexin antagonist), respectively, used agitation insomnia patients, As experimental investigations research progress, there possibility combination newly medications traditional ones may emerge promising option future.

Language: Английский

Citations

7
Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions DOI
Kaitlin A. Freeberg,

CeAnn C Udovich,

Christopher R. Martens

et al.

The Journals of Gerontology Series A, Journal Year: 2023, Volume and Issue: 78(12), P. 2435 - 2448

Published: April 17, 2023

Abstract Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance precursor compounds, such as riboside or mononucleotide, has profound effects on physiological function models of aging disease. Translation these compounds for oral supplementation humans been increasingly studied within the last 10 years; however, clinical evidence raising concentrations can improve is unclear. The goal this review was to synthesize published literature chronic precursors healthy age-related diseases. We identified riboside, co-administered pterostilbene, mononucleotide most common candidates investigations NAD+-boosting improving humans. Studies have performed generally midlife older adults, adults cardiometabolic risk factors overweight obesity, numerous patient populations. Supplementation safe, tolerable, increase related metabolites multiple tissues. Dosing regimens study durations vary greatly across interventions, small sample sizes limit data interpretation outcomes. Limitations future research directions suggested further our understanding potential efficacy extending human health span.

Language: Английский

Citations

15