Tracing ALS Degeneration: Insights from Spinal Cord and Cortex Transcriptomes DOI Open Access
Nela Pragathi Sneha,

S. Akila Parvathy Dharshini,

Y‐h. Taguchi

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(11), P. 1431 - 1431

Published: Nov. 2, 2024

Background/Objectives: Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons. Key factors contributing to neuronal death include mitochondrial energy damage, oxidative stress, excitotoxicity. The frontal cortex crucial for action initiation, planning, voluntary movements whereas spinal cord facilitates communication with brain, walking, reflexes. By investigating transcriptome data from cord, we aim elucidate common pathological mechanisms pathways involved in ALS understanding disease progression identifying potential therapeutic targets. Methods: In this study, quantified gene transcript expression patterns, predicted variants, assessed their functional effects using computational tools. It also includes predicting variant-associated regulatory effects, constructing interaction networks, performing enrichment analysis. Results: We found novel genes upregulation immune response, downregulation metabolic-related defective degradation processes both cortex. Additionally, observed dysregulation histone regulation blood pressure-related specifically Conclusions: These results highlight distinct shared molecular disruptions ALS, emphasizing critical roles response metabolic dysfunction degeneration. Targeting these may provide new avenues combat neurodegeneration preserve health.

Language: Английский

Non-Immune Functions of Innate Immunity Acting on Physiological Processes: Insights from Drosophila DOI Open Access
Xiaoyan Li, Xiaomin Wang, Zhen Shang

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1087 - 1087

Published: Jan. 27, 2025

As the first line of host immune defense, innate immunity plays a key role in warding off foreign pathogens and damage. Drosophila melanogaster, as classical model animal for more than 100 years, is an important research studying immunity. In recent scientists have made remarkable progress recognition mechanisms immunity, effector molecules, modes their response at cellular tissue levels. However, interaction between other physiological functions remains relatively novel has yet to be systematically explored. Here, we briefly discuss link system regulation, from several representative perspectives such sleep, insulin, brain function. Then, using model, provide overview specifically summarize on regulation physiology by covering lipid metabolism, development, neurodegenerative diseases, memory, feeding, lifespan, movement, antioxidation. This review provides valuable into how influences processes, providing deeper understanding complex roles underlying

Language: Английский

Citations

0
Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances DOI Open Access

Radu Eugen Rizea,

Antonio-Daniel Corlatescu, Horia Petre Costin

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9966 - 9966

Published: Sept. 15, 2024

This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well emerging treatments. The purpose is to condense key findings illustrate the complexity ALS, which shaped by both genetic environmental influences. We reviewed literature discuss recent advancements in understanding molecular mechanisms such protein misfolding, mitochondrial dysfunction, oxidative stress, axonal transport defects, are critical for identifying potential therapeutic targets. Significant progress has been made refining criteria biomarkers, leading earlier more precise diagnoses. Although drug treatments provide some benefits, there a clear need effective therapies. Emerging treatments, gene therapy stem cell therapy, show modifying disease progression improving quality life ALS patients. emphasizes importance continued research address challenges variability limited effectiveness existing Future should concentrate on further exploring foundations developing new approaches. implications practice include ensuring accessibility that healthcare systems equipped support ongoing patient care.

Language: Английский

Citations

3
Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage DOI Open Access
Lee J. Martin,

Shannon J. Koh,

Antionette Price

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 9106 - 9106

Published: Aug. 22, 2024

Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes degeneration of motor neurons (MNs) and paralysis. ALS can be caused by mutations in the gene encodes copper/zinc superoxide dismutase (SOD1). SOD1 known mostly as cytosolic antioxidant protein, but also nucleus non-transgenic (tg) human (hSOD1) tg mouse MNs. SOD1’s nuclear presence different cell types subnuclear compartmentations are unknown, functions SOD1. We examined hSOD1 localization DNA damage mice expressing mutated wildtype variants (hSOD1-G93A hSOD1-wildtype). studied patient-derived induced pluripotent stem (iPS) cells to determine undifferentiated differentiated In hSOD1-G93A hSOD1-wildtype mice, choline acetyltransferase (ChAT)-positive MNs had hSOD1, while ChAT, showed symptom-related loss ChAT. The interneurons preserved parvalbumin positivity mice. was seen less commonly spinal cord astrocytes and, notably, oligodendrocytes, emerged, oligodendrocytes increased mutant presence. Brain subcellular fractionation identified soluble extracts brain cord, concentrated chromatin extract only cord. Nuclear from cords altered protein nitration, footprinting peroxynitrite presence, intact strongly production well active NADPH oxidase marker, p47phox. comet assay progressively (6–14 weeks age) accumulated single-strand breaks. Ablation NCF1 gene, encoding p47phox, pharmacological inhibition with systemic treatment apocynin (10 mg/kg, ip) extended mean lifespan about 25% mitigated genomic progression. postmortem CNS, found glia; degenerating cases formed inclusions. Human iPS during directed differentiation MNs, SOD1-expressing failed establish MN levels. conclude has prominent central nervous system, perhaps adopting aberrant contexts participate pathobiology.

Language: Английский

Citations

1
Tracing ALS Degeneration: Insights from Spinal Cord and Cortex Transcriptomes DOI Open Access
Nela Pragathi Sneha,

S. Akila Parvathy Dharshini,

Y‐h. Taguchi

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(11), P. 1431 - 1431

Published: Nov. 2, 2024

Background/Objectives: Amyotrophic Lateral Sclerosis is a progressive neurodegenerative disorder characterized by the loss of upper and lower motor neurons. Key factors contributing to neuronal death include mitochondrial energy damage, oxidative stress, excitotoxicity. The frontal cortex crucial for action initiation, planning, voluntary movements whereas spinal cord facilitates communication with brain, walking, reflexes. By investigating transcriptome data from cord, we aim elucidate common pathological mechanisms pathways involved in ALS understanding disease progression identifying potential therapeutic targets. Methods: In this study, quantified gene transcript expression patterns, predicted variants, assessed their functional effects using computational tools. It also includes predicting variant-associated regulatory effects, constructing interaction networks, performing enrichment analysis. Results: We found novel genes upregulation immune response, downregulation metabolic-related defective degradation processes both cortex. Additionally, observed dysregulation histone regulation blood pressure-related specifically Conclusions: These results highlight distinct shared molecular disruptions ALS, emphasizing critical roles response metabolic dysfunction degeneration. Targeting these may provide new avenues combat neurodegeneration preserve health.

Language: Английский

Citations

0