Genome Instability & Disease, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 24, 2024
Language: Английский
Indian Journal of Clinical Biochemistry, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 13, 2025
Language: Английский
Citations
3
Genes, Journal Year: 2025, Volume and Issue: 16(3), P. 268 - 268
Published: Feb. 25, 2025
The mitochondria–telomere axis is recognized as an important factor in the processes of metabolism, aging and oncogenesis. MicroRNAs (miRNAs) play essential function this complex interaction, having impact on aspects such cellular homeostasis, oxidative responses apoptosis. In recent years, miRNAs have been found to be crucial for telomeric stability, well mitochondrial behavior, factors that influence cell proliferation viability. Furthermore, (mitomiRs) are associated with gene expression activity cGAS/STING pathway activity, linking DNA recognition immune system responses. Hence, maintain a link biogenesis, metabolic changes cancer organelles. This review focuses roles variety progression their potential application biomarkers or therapeutic agents.
Language: Английский
Citations
0
Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown
Published: March 26, 2025
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron degeneration in the primary cortex (PMC) and spinal cord. Aging key factor ALS onset progression, with evidence suggesting that biological aging-a process involving cellular decline- far outpaces chronological aging ALS. This promotes senescent cell accumulation-marked irreversible cell-cycle arrest, impaired apoptosis, chronic inflammation-disrupting tissue homeostasis impairing neuronal support functions. Thus, targeting senescence presents novel therapeutic strategy for Here, we investigated senolytic combination Dasatinib Quercetin (D&Q) TDP-43 Q331K mice. D&Q improved neuromuscular function reduced plasma neurofilament light chain, biomarker of axonal damage. The most pronounced improvement was cortical excitability, accompanied reductions PMC. These findings highlight potential senolytics to mitigate ALS-related dysfunction, supporting their viability as strategy. *Jose A. Viteriab, Nathan R. Kerrab, Charles D. Brennana are co-first authors.
Language: Английский
Citations
0
Journal of Affective Disorders, Journal Year: 2025, Volume and Issue: unknown
Published: March 1, 2025
Language: Английский
Citations
0
Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 410 - 410
Published: March 25, 2025
Background/Objectives: TDP-43 mutation-driven Amyotrophic Lateral Sclerosis (ALS) motor neuron disease is one of the most prominent forms (approximately 97%) in cases sporadic ALS. Dysfunctional autophagy and lysosomal function are prime mechanisms behind Mitoxantrone (Mito), a synthetic doxorubicin analog, an inhibitor DNA RNA synthesis/repair via intercalating with nitrogenous bases inhibiting topoisomerase II. The therapeutic potential miRNAs associated conditions has also been reported. This study explores Mito along against mutated protein-induced proteinopathy human-induced pluripotent stem cell (hiPSC)-derived human neural progenitor cells (hNPCs). Methods: HiPSCs for were differentiated into hNPCs used to explore at concentration 1 μM 24 h (the identified non-cytotoxic dose). effects on miRNA expression various cellular parameters such as mitochondrial dynamics, autophagy, stress granules assessed using high-throughput Open Array technique, immunocytochemistry, flow cytometry, immunoblotting, bioenergetic assay. Results: Mutated protein accumulation causes granule formation (G3BP1), dysfunction, SOD1 accumulation, hyperactivated ER hNPCs. show dysregulation six (miR-543, miR-34a, miR-200c, miR-22, miR-29b, miR-29c) A significant restoration mutation-induced alterations could be witnessed upon exposure Mito. Conclusions: Our indicates that miR-543, miR-34a have antisense alone combination Mitoxantrone.
Language: Английский
Citations
0
Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)
Published: Nov. 20, 2024
Understanding the interrelationship between gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over past decade. In context of brain disorders including those characterized by neurodevelopmental neurodegenerative changes there have been advances. However, initially research involved correlational analyses, had limited translational scope, lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation underlying mechanisms via depth analysis methods are needed. neurodegeneration research, strong causal evidence now links microbiome to Alzheimer's (AD), Parkinson's Disease (PD), as supported human-to-animal transplantation studies. Longitudinal interventions being conducted AD, PD, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis. Neurodevelopmental also seen a boon microbiome-related autism, Attention-deficit/hyperactivity disorder, schizophrenia, which is confirming prior animal model work regarding key time-windows for infant cognition. While recent advances represent progress, fundamental knowledge gaps obstacles remain. Knowing how why at extremes life will develop our mechanistic understanding help build base we strive toward counteracting microbial missteps with precision therapeutic interventions.
Language: Английский
Citations
2
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2024, Volume and Issue: 1871(6), P. 119753 - 119753
Published: May 18, 2024
Language: Английский
Citations
1
Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17
Published: Sept. 3, 2024
The progressive degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) is accompanied by the formation a broad array cytoplasmic and nuclear neuronal inclusions (protein aggregates) largely containing RNA-binding proteins such as TAR DNA-binding protein 43 (TDP-43) or fused sarcoma/translocated liposarcoma (FUS/TLS). This process driven liquid-to-solid phase separation generally from membrane-less organelles giving rise to pathological biomolecular condensates. these aggregates suggests fundamental alteration mRNA expression levels involved. Considering role epigenome gene expression, alterations DNA methylation, histone modifications, chromatin remodeling, non-coding RNAs, RNA modifications become highly relevant understanding how this takes effect. In review, we explore evidence that links epigenetic mechanisms with ALS. We propose greater inter-relates LLPS ALS will provide an attractive therapeutic target.
Language: Английский
Citations
1
Muscle & Nerve, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 7, 2024
Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. evolution of an extensive system appears restricted to human species, with ALS representing a uniquely disease. While some, very select non-human primates limited projections, these tend be absent in all other animals. From general perspective, early clinical features may considered reflect failure system. characteristic loss skilled motor dexterity involving limbs, speech impairment through progressive bulbar dysfunction specifically involve those units having strongest projections. A similar explanation likely underlies unique "split phenotypes" that now been well characterized ALS. Large Betz cells pyramidal projecting neurons, their dendritic arborization, are particularly vulnerable elements exposome such as aging, environmental stress lifestyle changes. Progressive proteosome impairs nucleocytoplasmic shuffling induces toxic but soluble TDP-43 aggregate corticomotoneurons. cell is further accentuated profuse arborizations. Clarification specific genomes neural networks will promote initiation precision medicine approaches directed key structure neurological manifestations ALS,
Language: Английский
Citations
1
Aging advances., Journal Year: 2024, Volume and Issue: 1(1), P. 42 - 51
Published: July 24, 2024
With aging, senescence-related diseases are increasing in prevalence. The senescence of cells the central nervous system has been linked with development neurodegenerative such as Alzheimer’s or Parkinson’s disease. These changes not limited to brain many eye diseases, cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma, also age-related. Among them, glaucoma is one leading causes irreversible blindness a multifactorial nature. Besides an elevated intraocular pressure, increased age main risk factors for this Hence, review, we will discuss context disease, specific focus on glaucoma. Several general aging mechanisms were put forward different diseases. This includes dysregulated nutrient sensing, cellular senescence, stem cell exhaustion, altered intercellular communication, genomic instability, telomere shortening, epigenetic alteration, loss proteostasis, compromised autophagy, mitochondrial dysfunction. In factor development. triggered by oxidative, metabolic, immunological, biomechanical stressors cross-talks. Oxidative stress, example, can trigger apoptotic death through damage, hypoxia, inflammation, endothelial dysregulation. Also, advanced age, alterations extracellular matrix composition structure becoming important contributing pathology All mentioned processes generally accepted aged eye. A better understanding these help find novel therapeutic approaches patients future.
Language: Английский
Citations
0