The long term effects of uncoupling interventions as a therapy for dementia in humans DOI Creative Commons
Alan G Holt, Adrian Davies

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 7, 2023

In this paper we use simulation methods to study a hypothetical uncoupling agent as therapy for dementia. We simulate the proliferation of mitochondrial deletion mutants amongst population wild-type in human neurons. Mitochondria play key role ATP generation. Clonal expansion can lead being overwhelmed by deletions such that diminished no longer fulfill cell's energy requirement, eventually leading its demise. The intention is reduce formation reducing mutation rate. However, consequence production efficacy also reduced which turn increases copy number order compensate deficit. results showed severity dementia, however, there was some increase cognitive dysfunction pre-onset effectiveness dependent upon timing intervention relative onset dementia and would necessitate predicting many years advance.

Language: Английский

Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities DOI Creative Commons
Vicente Javier Clemente‐Suárez, Laura Redondo-Flórez, Ana Isabel Beltrán-Velasco

et al.

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 7, 2023

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.

Language: Английский

Citations

65
Mitochondrial Transfer as a Novel Therapeutic Approach in Disease Diagnosis and Treatment DOI Open Access
Vicente Javier Clemente‐Suárez, Alexandra Martín-Rodríguez, Rodrigo Yañéz‐Sepúlveda

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8848 - 8848

Published: May 16, 2023

Mitochondrial dysfunction is a hallmark of numerous diseases, including neurodegenerative disorders, metabolic and cancer. transfer, the transfer mitochondria from one cell to another, has recently emerged as potential therapeutic approach for restoring mitochondrial function in diseased cells. In this review, we summarize current understanding its mechanisms, applications, impact on death pathways. We also discuss future directions challenges field novel disease diagnosis treatment.

Language: Английский

Citations

53
Review of Pharmacotherapeutic Targets in Alzheimer’s Disease and Its Management Using Traditional Medicinal Plants DOI Open Access
Prabhash Nath Tripathi,

Ankit Lodhi,

Sachchida Nand

et al.

Degenerative Neurological and Neuromuscular Disease, Journal Year: 2024, Volume and Issue: Volume 14, P. 47 - 74

Published: May 1, 2024

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there currently no cure for AD, several pharmacotherapeutic targets management strategies have been explored. Additionally, traditional medicinal plants gained attention their potential role in AD management. Pharmacotherapeutic include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, cholinergic dysfunction. Traditional plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), Panax ginseng, demonstrated the ability to modulate these through bioactive compounds. biloba , instance, contains flavonoids terpenoids that exhibit neuroprotective effects reducing Aβ deposition enhancing cerebral blood flow. serrata natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving function. enriched with curcumin, exhibits anti-inflammatory antioxidant effects, potentially mitigating neuroinflammation stress. ginseng's ginsenosides shown anti-amyloidogenic properties. The investigation complementary approach offers advantages, including lower risk adverse multi-target interactions. Furthermore, cultural knowledge utilization provide rich information development new therapies. However, further research necessary elucidate precise mechanisms action, standardize preparations, assess safety efficacy remedies. Integrating medicinal-plant-based therapies modern pharmacotherapies may hold key more comprehensive effective treatment. This review aims explore its Keywords: disease, acetylcholinesterase, amyloid beta, protein, medicine, Ayurvedic herbs, acetylcholinesterase inhibitors, disorders, cognition

Language: Английский

Citations

44
Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies DOI Creative Commons

Kyle C McGill Percy,

Zhenguo Liu, Xin Qi

et al.

Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00525 - e00525

Published: Jan. 1, 2025

Language: Английский

Citations

3
Mitochondrial Dysfunction as the Major Basis of Brain Aging DOI Creative Commons
Stephen C. Bondy

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 402 - 402

Published: March 26, 2024

The changes in the properties of three biological events that occur with cerebral aging are discussed. These adverse already begin to develop early mid-life and gradually become more pronounced senescence. Essentially, they reflections progressive decline effectiveness key processes, resulting deviation essential biochemical trajectories ineffective ultimately harmful variants these programs. emphasis this review is major role played by mitochondria transition important processes toward deleterious as brain proceeds. immune system: shift away from an efficient response a unfocused, continuing inflammatory condition. Such state both harmful. Reactive oxygen species intracellular signaling systems. Additionally, microglial phagocytic activity utilizing short lived reactive contribute removal aberrant or dead cells bacteria. transformed into excessive, untargeted, persistent generation pro-oxidant free radicals (oxidative stress). normal neural transmission modified undirected, chronic low-level excitatory activity. Each characterized occurrence continuous inefficient diffused. signal/noise ratio several critical thus reduced beneficial responses replaced their impaired variants.

Language: Английский

Citations

12
Mitochondria-Targeted Delivery Strategy of Dual-Loaded Liposomes for Alzheimer’s Disease Therapy DOI Open Access
Л. А. Васильева, Gulnara A. Gaynanova, Ф. Г. Валеева

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10494 - 10494

Published: June 22, 2023

Liposomes modified with tetradecyltriphenylphosphonium bromide dual loading of α-tocopherol and donepezil hydrochloride were successfully designed for intranasal administration. Physicochemical characteristics cationic liposomes such as the hydrodynamic diameter, zeta potential, polydispersity index within range from 105 to 115 nm, +10 +23 mV, 0.1 0.2, respectively. In vitro release curves analyzed using Korsmeyer-Peppas, Higuchi, First-Order, Zero-Order kinetic models. Nanocontainers surfactant statistically better penetrate into mitochondria rat motoneurons. Imaging brain slices revealed penetration nanocarriers brain. Experiments on transgenic mice an Alzheimer's disease model (APP/PS1) demonstrated that administration 21 days resulted in enhanced learning abilities a reduction formation rate Aβ plaques entorhinal cortex hippocampus

Language: Английский

Citations

21
Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders DOI Creative Commons
George Anderson, Abbas F. Almulla, Rüssel J. Reiter

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(9), P. 1237 - 1237

Published: April 25, 2023

Although previously restricted to a limited number of medical conditions, there is growing appreciation that 'autoimmune' (or immune-mediated) processes are important aspects wide array diverse including cancers, neurodegenerative diseases and psychiatric disorders. All these classes conditions associated with alterations in mitochondrial function across an cell types. Accumulating data indicate the presence melatonergic pathway possibly all body cells, consequences for pathways crucial driving CD8+ T B-cell 'autoimmune'-linked processes. Melatonin suppression coupled upregulation oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising levels major histocompatibility complex (MHC)-1, which underpins chemoattraction cells activation antibody-producing B-cells. Many factors closely autoimmunity, gut microbiome/permeability, circadian rhythms, aging, aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) its receptor tyrosine B (TrkB) interact pathway. A future research directions novel treatment implications indicated this collection poorly conceptualized treated presentations. It proposed etiology many 'autoimmune'/'immune-mediated' disorders should be as significantly determined by dysregulation, being aspect pathoetiologies.

Language: Английский

Citations

14
Mitochondrial Aconitase and Its Contribution to the Pathogenesis of Neurodegenerative Diseases DOI Open Access
Volodymyr Padalko, Filip Posnik, Małgorzata Adamczyk

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9950 - 9950

Published: Sept. 15, 2024

This survey reviews modern ideas on the structure and functions of mitochondrial cytosolic aconitase isoenzymes in eukaryotes. Cumulative experimental evidence about aconitases (Aco2) as one main targets reactive oxygen nitrogen species is generalized. The important role Aco2 maintenance homeostasis intracellular iron pool DNA discussed. pathogenesis some neurodegenerative diseases highlighted. Inactivation or dysfunction well mutations found ACO2 gene appear to be significant factors development promotion various types diseases. A restoration efficient functioning a source energy for cell by targeting seems promising therapeutic directions minimize progressive disorders.

Language: Английский

Citations

5
Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling DOI Creative Commons
Xiaoqing Huang,

Asha Jacob Jannu,

Ziyan Song

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Deciphering the diverse molecular mechanisms in living Alzheimer's disease (AD) patients is a big challenge but pivotal for prognosis and precision medicine development. Utilizing an optimal transport approach, we conducted graph-based mapping of transcriptomic profiles to transfer AD subtype labels from ROSMAP monocyte samples ADNI ANMerge peripheral blood mononuclear cells. Subsequently, differential expression followed by comparative pathway diffusion pseudotime analysis were applied each cohort infer progression trajectories. Survival with real follow-up time was used obtain potential biomarkers prognosis. accurately transferred onto patients. Pathways associated genes neutrophil degranulation-like immune process, acute phase response, IL-6 signaling significantly progression. The work enhanced our understanding different subtypes, offering insights into personalized interventions improved patient care. We innovative transport-based approach map data studies known cell (PBMC) within cohorts. Through comprehensive trajectory analysis, investigated underlying trajectories AD. validated accuracy label identified prognostic genetic markers progression, facilitating treatment strategies. By identifying predicting distinctive subtypes their pathways, study contributes deeper heterogeneity.

Language: Английский

Citations

0
Qiangji Decoction mitigates neuronal damage, synaptic and mitochondrial dysfunction in SAMP8 mice through the regulation of ROCK2/Drp1-mediated mitochondrial dynamics DOI

Bixuan Lai,

Dan Wu, Qiang Xiao

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119424 - 119424

Published: Jan. 1, 2025

Language: Английский

Citations

0