Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(17), С. 13033 - 13033

Опубликована: Авг. 22, 2023

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death neurons, leading to range neurological symptoms. Despite heterogeneity these conditions, common denominator is implication mitochondrial dysfunction in their pathogenesis. Mitochondria play crucial role creating biomolecules, providing energy through adenosine triphosphate (ATP) generated oxidative phosphorylation (OXPHOS), producing reactive oxygen species (ROS). When they’re not functioning correctly, becoming fragmented losing membrane potential, they contribute diseases. In this review, we explore how mitochondria fuse undergo fission, especially context NDs. We discuss genetic protein mutations linked impact dynamics. also look at key regulatory proteins fusion (MFN1, MFN2, OPA1) fission (DRP1 FIS1), including post-translational modifications. Furthermore, highlight potential drugs that can influence By unpacking complex processes, aim direct research towards treatments improve life quality for people with challenging conditions.

Язык: Английский

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Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance

Ageing Research Reviews, Год журнала: 2024, Номер 99, С. 102357 - 102357

Опубликована: Июнь 1, 2024

Neurodegenerative disorders (NDs) are expected to pose a significant challenge for both medicine and public health in the upcoming years due global demographic changes. NDs mainly represented by degeneration/loss of neurons, which is primarily accountable severe mental illness. This neuronal degeneration leads many neuropsychiatric problems permanent disability an individual. Moreover, tight junction brain, blood-brain barrier (BBB)has protective feature, functioning as biological that can prevent medicines, toxins, foreign substances from entering brain. However, delivering any medicinal agent brain (i.e., Multiple sclerosis, Alzheimer's, Parkinson's, etc.) enormously challenging. There approved therapies address NDs, but most them only help treat associated manifestations. The available have failed control progression certain factors, i.e., BBB drug-associated undesirable effects. extremely complex pathology, with pathogenic mechanisms involved initiation progression; thereby, limited survival rate has been observed ND patients. Hence, understanding exact mechanism behind crucial developing alternative approaches improving patients' rates. Thus, present review sheds light on different cellular novel therapeutic their clinical relevance, will assist researchers alternate strategies limitations conventional therapies. current work offers scope into near future improve approach NDs.

Язык: Английский

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Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 14

Опубликована: Фев. 16, 2024

Abnormal behavior of α-synuclein and prion proteins is the hallmark Parkinson’s disease (PD) illnesses, respectively, being complex neurological disorders. A primary cause protein aggregation, brain injury, cognitive loss in illnesses misfolding normal cellular (PrP C ) into an infectious form Sc ). Aggregation causes disruptions processes (PD), leading to dopamine-producing neurons motor symptoms. Alteration composition or activity gut microbes may weaken intestinal barrier make it possible for prions go from brain. The gut-brain axis linked neuroinflammation; metabolites produced by microbiota affect aggregation α-synuclein, regulate inflammation immunological responses, influence course neurotoxicity proteins, even if their targets are distinct proteins. This thorough analysis explores interactions that exist between neurodegenerative particularly involvement microbiota, a collection bacteria, archaea, fungi, viruses etc., various becoming increasingly recognized. microbiome influences neuroinflammation, neurotransmitter synthesis, mitochondrial function, integrity through axis, which contributes development progression disease. review delves molecular mechanisms underlie these relationships, emphasizing effects microbial such as bacterial lipopolysaccharides (LPS), short-chain fatty acids (SCFAs) regulating functioning. Additionally, looks at how environmental dietary decisions whether they could be risk factors illnesses. study concludes highlighting critical role plays It also provides promising direction future research treatment approaches. People afflicted difficult ailments find hope new preventive therapeutic approaches diseases better understood.

Язык: Английский

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Targeting Mitochondrial Dysfunction in Cerebral Ischemia: Advances in Pharmacological Interventions

Antioxidants, Год журнала: 2025, Номер 14(1), С. 108 - 108

Опубликована: Янв. 18, 2025

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation reactive oxygen species (ROS), calcium homeostasis, and execution apoptotic processes. Disruptions function, driven by factors such as oxidative stress, excitotoxicity, altered ion balance, lead to neuronal death contribute cognitive impairments several brain diseases. Mitochondrial can arise from genetic mutations, ischemic events, hypoxia, other environmental factors. This article highlights critical role progression diseases discusses need targeted therapeutic strategies attenuate damage, restore enhance neuroprotection.

Язык: Английский

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The Potential of Superoxide Dismutase-Rich Tetraselmis chuii as a Promoter of Cellular Health

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1693 - 1693

Опубликована: Фев. 16, 2025

Tetraselmis chuii (T. chuii) is a green, marine, eukaryotic, microalgae that was authorized in the European Union (EU) as novel food for human consumption 2014, and supplement 2017. This narrative review will provide an overview of preclinical clinical trials assessing efficacy T. chuii-derived ingredient, characterized by high superoxide dismutase (SOD) activity (SOD-rich chuii), to improve various aspects cellular health. Collectively, results from vitro, more importantly vivo research, support SOD-rich potential promoter Principally, ingredient appears function indirect antioxidant boosting intracellular systems. Moreover, it can positively modulate inflammatory status up-regulating anti-inflammatory down-regulating pro-inflammatory cytokines factors. In addition, promote health though protecting DNA damage, immune function, strengthening cell structure integrity, modulating signaling pathways. There also some evidence suggest may mitochondrial through up-regulation genes linked biogenesis ATP synthesis. From conducted date, transcriptional activation nuclear factor erythroid 2-related 2 (NRF2) sirtuin 1 (SIRT1) appear be important mediating effects on These exciting preliminary observations represent natural blue with enhance

Язык: Английский

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How did antibiotic growth promoters increase growth and feed efficiency in poultry?

Poultry Science, Год журнала: 2023, Номер 103(2), С. 103278 - 103278

Опубликована: Ноя. 17, 2023

It has been hypothesized that reducing the bioenergetic costs of gut inflammation as an explanation for effect antibiotic growth promoters (AGPs) on animal efficiency, framing some observations but not explaining increase in rate or prevention infectious diseases. The host's ability to adapt alterations environmental conditions and maintain health involves managing all physiological interactions regulate homeostasis. Thus, metabolic pathways are vital regulating energetic demands host guides most biological functions. Mitochondria only heart cell because their role energy metabolism oxidative phosphorylation, also a central hub signal transduction receive messages about nutritional states cells tissues. In response, mitochondria direct cellular tissue throughout host. endosymbiotic theory suggests evolved from prokaryotes, emphasizing idea these organelles can be affected by antibiotics. Indeed, therapeutic levels several antibiotics toxic mitochondria, subtherapeutic may improve mitochondrial function defense mechanisms inducing adaptive response cell, resulting mitokine production which coordinates array responses stressor(s). This stress is observed bacteria species, suggesting this protective mechanism preserved during evolution. Concordantly, microbiome modulation sub-inhibitory concentration AGPs could result stimulation rather than inhibition determined microbial species. eukaryotes, internal external conditions, promote organism evolutionary strategy overcome potential negative conditions. We hypothesize indirect AGP regulation functional output homeostatic control manner similar those involved with disease tolerance.

Язык: Английский

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An insight into the anticancer potentials of lignan arctiin: A comprehensive review of molecular mechanisms

Heliyon, Год журнала: 2024, Номер 10(12), С. e32899 - e32899

Опубликована: Июнь 1, 2024

Natural products are being developed as possible treatment options due to the rising prevalence of cancer and harmful side effects synthetic medications. Arctiin is a naturally occurring lignan found in numerous plants exhibits different pharmacological activities, along with cancer. To elucidate anticancer properties underlying mechanisms action, comprehensive search various electronic databases was conducted using appropriate keywords identify relevant publications. The findings suggest that arctiin against tumor formation cancers such cervical, myeloma, prostate, endothelial, gastric, colon several preclinical investigations. This compound exerts its effect through cellular mechanisms, including mitochondrial dysfunction, cell cycle at phases (G2/M), inhibition proliferation, apoptotic death, cytotoxic effects, well migration invasion malignant cells. Moreover, study also revealed that, among pathways, shown be more potent terms PI3K/AKT JAK/STAT signaling pathways. However, pharmacokinetic investigation indicated compound's poor oral bioavailability. Because these findings, might considered promising chemotherapeutic drug candidate.

Язык: Английский

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Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches

Antioxidants, Год журнала: 2024, Номер 13(8), С. 906 - 906

Опубликована: Июль 26, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty (NAFLD), encompasses a range of conditions from steatosis to steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis MASLD involves dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role dysfunction in MASLD's progression. Therapeutically, enhancing function has gained interest, along lifestyle changes and pharmacological interventions targeting processes. FDA's approval resmetirom for metabolic-associated (MASH) fibrosis marks significant step. While represents progress, further research is essential understand MASLD-related fully. Innovative strategies like gene editing small-molecule modulators, alongside interventions, can potentially improve treatment. Drug repurposing new targets will advance therapy, addressing increasing burden. Therefore, this review aims provide better understanding identify more effective preventive treatment strategies.

Язык: Английский

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Mitochondrial plasticity and synaptic plasticity crosstalk; in health and Alzheimer's disease

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(8)

Опубликована: Авг. 1, 2024

Abstract Synaptic plasticity is believed to underlie the cellular and molecular basis of memory formation. Mitochondria are one main organelles involved in metabolism energy maintenance as plastic that change morphologically functionally response needs regulate synaptic function through multiple mechanisms, including ATP generation, calcium homeostasis, biogenesis. An increased neuronal activity enhances efficiency, during which mitochondria's spatial distribution morphology significantly. These build up pre‐and postsynaptic zones produce ATP, necessary for several processes like neurotransmitter release recycling. also homeostasis by buffering intracellular calcium, ensures proper activity. Furthermore, mitochondria presynaptic terminal have distinct morphological properties compared dendritic or mitochondria. This specialization enables precise control plasticity. Mitochondrial dysfunction has been linked failure many neurodegenerative disorders, Alzheimer's disease (AD). In AD, malfunctioning cause delays vesicle recycling, ionic gradient imbalances, mostly failure. review emphasizes mitochondrial plasticity's contribution function. It explores profound effect malfunction on focusing provides an overview how they sustain health under normal conditions their contributes diseases, highlighting potential a therapeutic target such conditions.

Язык: Английский

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Unraveling the role and mechanism of mitochondria in postoperative cognitive dysfunction: a narrative review

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Ноя. 12, 2024

Abstract Postoperative cognitive dysfunction (POCD) is a frequent neurological complication encountered during the perioperative period with unclear mechanisms and no effective treatments. Recent research into pathogenesis of POCD has primarily focused on neuroinflammation, oxidative stress, changes in neural synaptic plasticity neurotransmitter imbalances. Given high-energy metabolism neurons their critical dependency mitochondria, mitochondrial directly affects neuronal function. Additionally, as primary organelles generating reactive oxygen species, mitochondria are closely linked to pathological processes neuroinflammation. Surgery anesthesia can induce dysfunction, increase disrupt quality-control via various pathways, hence serving key initiators process. We conducted review role potential postoperative by consulting relevant literature from PubMed EMBASE databases spanning past 25 years. Our findings indicate that surgery inhibit respiration, thereby reducing ATP production, decreasing membrane potential, promoting fission, inducing calcium buffering abnormalities iron accumulation, inhibiting mitophagy, increasing stress. Mitochondrial damage ultimately lead impaired function, abnormal transmission, synthesis release neurotransmitters, even death, resulting dysfunction. Targeted therapies have shown positive outcomes, holding promise novel treatment for POCD.

Язык: Английский

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