Can melatonin improve the alteration of protein synthesis occurring in schizophrenia and bipolar disorder? DOI Creative Commons
Ana Coto‐Montes, Nerea Menéndez-Coto, José Antonio Boga

et al.

Melatonin Research, Journal Year: 2023, Volume and Issue: 6(1), P. 51 - 58

Published: Feb. 28, 2023

The prevalence of mental illnesses has significantly increased globally in recent decades due to multifactorial causes. Of these, schizophrenia and bipolar disorder, their high incidence associated disability, stand out. However, the effective treatments on these disorders are lagged behind incidence. Melatonin, as an essential molecule regulation sleep-wake rhythm naturally occurring antioxidant, only received attention for treatment such psychiatric relation its circadian regulation, but overwhelming role a regulator oxidative stress that facilitates amelioration neuronal damage not been addressed this respect. In communication, novel aspects melatonin have discussed. We provide necessary literature justify beneficial roles mechanisms treat disorder. These include enhances reticulum stress, potentiates unfolded protein response, increases endoplasmic synthesis facilitate autophagy even suppresses apoptosis. This process involves expected organelles is more complex cohesion includes mitochondria, well-known target melatonin, which reinforces robustness our hypothesis, i.e., prevents development aggregates abnormal structures typically observed brain damage. Its documented capacity need improve efficiency growing population afflicted by basis hypothesis support disorders.

Language: Английский

Purifying and profiling lysosomes to expand understanding of lysosomal dysfunction–associated diseases DOI Creative Commons
Ali Shilatifard, Issam Ben‐Sahra

Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: 135(4)

Published: Feb. 16, 2025

Lysosome storage dysfunction plays a central role in numerous human diseases, but lack of appropriate tools has hindered lysosomal content profiling clinical settings. In this issue the JCI, Saarela et al. introduce method called tagless LysoIP that enabled rapid isolation intact lysosomes from blood and brain cells via immunoprecipitation endogenous protein TMEM192. Applied to neurodegenerative disorder known as Batten disease (caused by mutations CLN3 gene), revealed substantial accumulation glycerophosphodiesters (GPDs) patient lysosomes. These findings highlight GPD clearance present an innovative will enable biomarker discovery therapeutic advancement diseases.

Language: Английский

Citations

0
Mitophagy in Alzheimer's disease and other metabolic disorders: a focus on mitochondrial-targeted therapeutics DOI

Shadt Skawratananond,

Daniel X Xiong,

Charlie Zhang

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102732 - 102732

Published: March 1, 2025

Language: Английский

Citations

0
Toxoplasma GRA16 attenuates tau hyperphosphorylation and enhances autophagy in thrombin-treated HT-22 hippocampal neuronal cells DOI Creative Commons
Seung‐Hwan Seo,

Do-Won Ham,

Ji‐Eun Lee

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract This study investigated whether Toxoplasma gondii-derived dense granule protein 16 (GRA16) modulates tau to attenuate hyperphosphorylation and promotes autophagy facilitate the removal of aggregates. HT-22 murine hippocampal neuronal cells were treated with thrombin induce rapid hyperphosphorylations aggregation. Thrombin increased hyperphosphorylated levels activated NF-κB, contributing pathology neuroinflammation. NF-κB activation apolipoprotein E (APOE) expression decreased forkhead box O3A (FOXO3A) expression, a factor involved in regulation, consequently limiting autophagy-related genes directly regulated by FOXO3A. Meanwhile, GRA16-transfected thrombin, GRA16 upregulated proteins dephosphorylation but downregulated phosphorylation. Moreover, inhibited thrombin-induced FOXO3A levels, thereby enhancing genes, including those enhanced intracellular autophagic flux thrombin-treated cells, as evidenced fluorescence significant reductions phosphorylated intensity. These findings suggest that possesses therapeutic potential tauopathies autophagy-mediated clearance, establishing conceptual foundation for developing new approaches targeting pathology.

Language: Английский

Citations

0
Autophagy: a double-edged sword in ischemia–reperfusion injury DOI Creative Commons
Laura H. Tang,

Wangzheqi Zhang,

Liao Yan

et al.

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: April 7, 2025

Abstract Ischemia–reperfusion (I/R) injury describes the pathological process wherein tissue damage, initially caused by insufficient blood supply (ischemia), is exacerbated upon restoration of flow (reperfusion). This phenomenon can lead to irreversible damage and commonly observed in contexts such as cardiac surgery stroke, where temporarily obstructed. During ischemic conditions, anaerobic metabolism tissues organs results compromised enzyme activity. Subsequent reperfusion exacerbates mitochondrial dysfunction, leading increased oxidative stress accumulation reactive oxygen species (ROS). cascade ultimately triggers cell death through mechanisms autophagy mitophagy. Autophagy constitutes a crucial catabolic mechanism within eukaryotic cells, facilitating degradation recycling damaged, aged, or superfluous organelles proteins via lysosomal pathway. essential for maintaining cellular homeostasis adapting diverse conditions. As self-degradation clearance mechanism, exhibits dualistic function: it confer protection during initial phases injury, yet potentially exacerbate later stages. paper aims elucidate fundamental I/R highlighting its dual role regulation effects on both organ-specific systemic responses. By comprehending their implications organ function, this study seeks explore potential therapeutic interventions modulation clinical settings.

Language: Английский

Citations

0
Sex and region-specific disruption of autophagy and mitophagy in Alzheimer’s disease: linking cellular dysfunction to cognitive decline DOI Creative Commons

Aida Adlimoghaddam,

Fariba Fayazbakhsh, Mohsen Mohammadi

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 26, 2025

Abstract Macroautophagy and mitophagy are critical processes in Alzheimer’s disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, not fully understood. This study investigates autophagic (LC3B-II, SQSTM1) mitophagic (BNIP3L, BNIP3, BCL2L13) markers the cortex hippocampus of male female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), tests (novel object recognition novel placement). Significant differences emerged: mice exhibited autophagosome accumulation due impaired degradation cortex, while males showed fewer autophagosomes, especially hippocampus, without significant changes. TEM analyses demonstrated variations mitochondrial mitophagosome numbers correlated with memory outcomes. Females had enhanced mitophagy, higher BNIP3L BCL2L13 levels, whereas elevated BNIP3 dimers. Cognitive deficits females dysfunction males, LC3B-II levels associated positively cognitive performance, suggesting protective autophagy effects. Using machine learning, we predicted based on data, pioneering a predictive approach cellular outcomes AD. These findings underscore importance regulation AD support personalized therapeutic approaches targeting these pathways. Integrating learning emphasizes its potential advance neurodegenerative research.

Language: Английский

Citations

0
Tau protein aggregation: A therapeutic target for neurodegenerative diseases DOI

Aryan Duggal,

Drishti Mahindru,

Kirti Baghel

et al.

Advances in protein chemistry and structural biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Toxoplasma GRA16 attenuates Tau hyperphosphorylation and enhances autophagy in thrombin-treated HT-22 hippocampal neuronal cells DOI Creative Commons
Seung‐Hwan Seo,

Do-Won Ham,

J. M. Lee

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 20, 2025

Language: Английский

Citations

0
Autophagy Activation Promoted by Pulses of Light and Phytochemicals Counteracting Oxidative Stress during Age-Related Macular Degeneration DOI Creative Commons

Roberto Pinelli,

Michela Ferrucci, Francesca Biagioni

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(6), P. 1183 - 1183

Published: May 30, 2023

The seminal role of autophagy during age-related macular degeneration (AMD) lies in the clearance a number reactive oxidative species that generate dysfunctional mitochondria. In fact, oxygen (ROS) retina misfolded proteins, alter lipids and sugars composition, disrupt DNA integrity, damage cell organelles produce retinal inclusions while causing AMD. This explains why pigment epithelium (RPE), mostly at level, is essential AMD even baseline conditions to provide powerful fast replacement oxidized molecules ROS-damaged When impaired within RPE, deleterious effects ROS, which are produced excess also conditions, no longer counteracted, may occur. Within can be induced by various stimuli, such as light naturally occurring phytochemicals. Light phytochemicals, turn, synergize enhance autophagy. explain beneficial pulses combined with phytochemicals both improving structure visual acuity. ability activate some further extend synergism degeneration. this way, photosensitive natural compounds light-dependent antioxidant

Language: Английский

Citations

9
The innate immune response in tauopathies DOI Creative Commons
Alexis M. Johnson, John R. Lukens

European Journal of Immunology, Journal Year: 2023, Volume and Issue: 53(6)

Published: March 18, 2023

Abstract Tauopathies, which include frontotemporal dementia, Alzheimer's disease, and chronic traumatic encephalopathy, are a class of neurological disorders resulting from pathogenic tau aggregates. These aggregates disrupt neuronal health function leading to the cognitive physical decline tauopathy patients. Genome‐wide association studies clinical evidence have brought light large role immune system in inducing driving tau‐mediated pathology. More specifically, innate genes found harbor risk alleles, pathways upregulated throughout course disease. Experimental has expanded on these findings by describing pivotal roles for regulation kinases In this review, we summarize literature implicating as drivers tauopathy.

Language: Английский

Citations

8
Parkin-mediated mitophagy protects against aluminum trichloride-induced hippocampal apoptosis in mice via the mtROS-NLRP3 pathway DOI Creative Commons
Siming Huo, Xuliang Zhang,

Jinyu Xu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 264, P. 115459 - 115459

Published: Sept. 11, 2023

Aluminum is a neurotoxic food contaminant. trichloride (AlCl3) causes hippocampal mitochondrial damage, leading to injury. Damaged mitochondria can release reactive oxygen species (mtROS) and activate nucleotide-binding oligomerization domain-like receptor-containing 3 (NLRP3) inflammasomes apoptosis. E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy attenuate damage. However, the role of in AlCl3-induced mice damage its regulatory mechanism remain elusive. First, C57BL/6 N were treated with 0, 44.825, 89.65, 179.3 mg/kg body weight AlCl3 drinking water for 90 d. Apoptosis, NLRP3-inflammasome activation increased In addition, Parkin-mediated peaked middle-dose group was slightly attenuated high-dose group. Subsequently, we used wild-type Parkin knockout (Parkin-/-) investigate The results showed that Parkin-/- inhibited mitophagy, aggravated activation, apoptosis Finally, administered MitoQ (mtROS inhibitor) MCC950 (NLRP3 AlCl3-treated mitophagy. inhibition mtROS NLRP3 apoptosis, mice. These findings indicate protects against via mtROS-NLRP3 pathway.

Language: Английский

Citations

7