Mitochondrial-based therapies for neurodegenerative diseases: a review of the current literature

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Abstract Neurodegenerative disorders present significant challenges to modern medicine because of their complex etiology, pathogenesis, and progressive nature, which complicate practical treatment approaches. Mitochondrial dysfunction is an important contributor the pathophysiology various neurodegenerative illnesses, including Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS). This review paper examines current literature highlighting multifaceted functions mitochondria, energy production, calcium signaling, apoptosis regulation, mitochondrial biogenesis, dynamics, axonal transport, endoplasmic reticulum–mitochondrial interactions, mitophagy, proteostasis, crucial involvement in neuronal health. The emphasizes increasing recognition as a critical factor progression disorders, marking shift from traditional symptom management innovative mitochondrial-based therapies. By discussing mechanisms, quality control (MQC) processes impact oxidative stress, this highlights need for novel therapeutic strategies restore function, protect connections integrity, slow progression. comprehensive aims provide insights into potential interventions that could transform landscape diseases, addressing symptoms underlying pathophysiological changes.

Язык: Английский

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Neuroinflammation and energy metabolism: a dual perspective on ischemic stroke

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 10, 2025

Ischemic stroke is a prevalent form of cerebrovascular accident, with its pathogenesis involving the intricate interplay between neuroinflammation and energy metabolism. Cerebral ischemia disrupts oxygen supply, triggering metabolic dysregulation activating neuroinflammatory responses, ultimately resulting in cellular damage. This review provides an exhaustive analysis complex mechanisms ischemic stroke, particular focus on interaction The interruption supply due to cerebral initiates activates including release inflammatory cytokines activation immune cells, contributing damage further disturbances. Studies indicate that metabolism significantly impairs neural cell function interacts neuroinflammation, exacerbating brain injury. Therapeutic strategies primarily concentrate modulating suppressing emphasizing importance in-depth research into their provide theoretical foundation for new treatment stroke. Future should how balance anti-inflammatory regulation minimize promote recovery.

Язык: Английский

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β -hydroxybutyrate enhances brain metabolism in normoglycemia and hyperglycemia, providing cerebroprotection in a mouse stroke model

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Апрель 12, 2025

Hyperglycemia in poorly controlled diabetes is widely recognized as detrimental to organ dysfunction. However, the acute effects of hyperglycemia on brain metabolism and function are not fully understood. The potential protective benefit ketone bodies mitochondrial has also been well characterized. Here, we evaluated β-hydroxybutyrate (BHB) by employing a novel approach leveraging adenosine triphosphate (ATP)-dependence bioluminescence originating from luciferin-luciferase activity. Oxygen consumption rate was measured ex vivo live punches further evaluate function. Our data demonstrate that mice affected exposure high glucose. This short-term effect glucose reduced co-administration with body BHB. Additionally, investigated functional relevance BHB using an photothrombotic stroke model assess its cerebroprotective presence or absence hyperglycemia. significantly infarct size model, providing evidence for role brain. These findings suggest may effectively mitigate adverse metabolic stress ischemic events

Язык: Английский

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The role of the “gut microbiota-mitochondria” crosstalk in the pathogenesis of multiple sclerosis

Frontiers in Microbiology, Год журнала: 2024, Номер 15

Опубликована: Апрель 29, 2024

Multiple Sclerosis (MS) is a neurologic autoimmune disease whose exact pathophysiologic mechanisms remain to be elucidated. Recent studies have shown that the onset and progression of MS are associated with dysbiosis gut microbiota. Similarly, large body evidence suggests mitochondrial dysfunction may also significant impact on development MS. Endosymbiotic theory has found human mitochondria microbial in origin share similar biological characteristics Therefore, microbiota function crosstalk relevant However, relationship between not fully understood. by synthesizing previous literature, this paper focuses changes metabolite composition possible MS, provide new therapeutic approaches for prevention or reduction based crosstalk.

Язык: Английский

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Flow Cytometric Evaluation of Mitochondrial Health

Опубликована: Янв. 1, 2025

Язык: Английский

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Schisandrin B Improves Mitochondrial Function and Inhibits HT22 Cell Apoptosis by Regulating Sirt3 Protein

The Journal of Membrane Biology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Язык: Английский

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Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux

Autophagy, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

The CGG repeat expansions in the 5"-UTR regions of certain genes have been implicated various neurodegenerative and muscular disorders. However, underlying pathogenic mechanisms are not well understood. In this study, we explore role small molecular chaperone HSPB1 counteracting neurodegeneration induced by poly-glycine (poly-G) aggregates. Employing a reporter system, demonstrate that within GIPC1 gene produce poly-G proteins, repeat-associated non-AUG (RAN) translation. Through proximity labeling subsequent mass spectrometry analysis, characterize composition insoluble aggregates reveal these sequester key macroautophagy/autophagy receptors, SQSTM1/p62 TOLLIP. This sequestration disrupts MAP1LC3/LC3 recruitment impairs autophagosome formation, thereby compromising autophagic pathway. Importantly, show facilitates dissociation receptors from consequently restores function. Overexpressing alleviates poly-G-induced mouse models. Taken together, findings highlight mechanistic basis for neuroprotective effects suggest its potential as therapeutic target treating poly-G-associated diseases.

Язык: Английский

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Mapping brain neural networks in stress brain connectivity

Progress in brain research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Discovery of Novel 2‐Oxindoles as Compounds with Antiglaucoma Activity

ChemMedChem, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

We have synthesized new melatonin analogs 4,6,11,12 based on 3-hydroxy-2-oxindoles (11) and hydroxy-free 2-oxindoles (4,6,12) evaluated their neuroprotective antioxidant properties as well ability to reduce intraocular pressure. Reductive amination was used obtain 5-(benzylamino)-substituted (indolin-3-yl)acetonitriles 11 (indolin-3-yl)acetic acids 12 with high yields. Compounds 4a,c, 6a 11a,d,h,j-l demonstrated IOP reduction effect in range 15-27% similar the of reference compounds timolol (12% 18%, respectively). 5-(Benzylamino)-substituted 11, unlike 4,6, inhibited lipid peroxidation 2.075-13.012 µM. Inhibition NQO2 associated also for it found that compound 11h showed best inhibitory activity an IC50 = 39 μM (vs. 64 μM). All at a concentration 30 µM do not possess mitochondrial toxicity. Moreover, no disruption tubulin polymerization observed even presence 100 compounds. Thus, 3-hydroxy-2-oxindole derivatives can be drug design first-in-class antiglaucoma drugs properties.

Язык: Английский

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Mitochondria targeted nanoparticles for the treatment of mitochondrial dysfunction-associated brain disorders

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 13

Опубликована: Март 12, 2025

Mitochondria play a significant role in several cellular activities and their function health disease has become an important area of research. Since the brain is high-energy-demanding organ, it particularly vulnerable to mitochondrial dysfunction. This been implicated disorders including neurodegenerative, psychiatric neurological disorders, e.g., Parkinson’s schizophrenia. Significant efforts are underway develop mitochondria-targeting pharmaceutical interventions. However, complex membrane network restricts entry therapeutic compounds into matrix. Nanoparticles (NPs) present novel solution this limitation, while also increasing stability moieties improving bioavailability. article provides detailed overview studies that have investigated treatment dysfunction using either targeted or non-targeted NPs as drug delivery systems. All showed improved functioning reduction reactive oxygen species (ROS) production, improvement overall respiration reversal toxin-induced damage. mitochondrial-targeted advantage over they were able improve rescue dynamics biogenesis, required lower concentration vivo dosage load show effect. Consequently, mitochondria-targeted promising approach. Future should exploit advances nanotechnology, neuroscience chemistry design can cross blood-brain barrier selectively target dysfunctional mitochondria, outcomes.

Язык: Английский

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