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

Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues DOI Creative Commons

Niyatee Samudra,

Courtney Lane‐Donovan, Lawren VandeVrede

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(12)

Published: June 14, 2023

Tauopathies are disorders associated with tau protein dysfunction and insoluble accumulation in the brain at autopsy. Multiple lines of evidence from human disease, as well nonclinical translational models, suggest that has a central pathologic role these disorders, historically thought to be primarily related gain toxic function. However, number tau-targeting therapies various mechanisms action have shown little promise clinical trials different tauopathies. We review what is known about biology, genetics, therapeutic been tested date. discuss possible reasons for failures therapies, such use imperfect models do not predict effects drug development; heterogeneity pathologies which may lead variable responses therapy; ineffective mechanisms, targeting wrong species or epitope. Innovative approaches can help address some difficulties plagued our field's development thus far. Despite limited success date, we continue refine understanding tau's pathogenic mechanism(s) neurodegenerative diseases, remain optimistic will eventually play treatment

Language: Английский

Citations

55
Mitochondria in Alzheimer’s Disease Pathogenesis DOI Creative Commons
Allison B. Reiss,

Shelly Gulkarov,

Benna Jacob

et al.

Life, Journal Year: 2024, Volume and Issue: 14(2), P. 196 - 196

Published: Jan. 30, 2024

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years above. It causes dementia with memory loss deterioration in thinking language skills. AD characterized by specific pathology resulting from the accumulation brain of extracellular plaques amyloid-β intracellular tangles phosphorylated tau. The importance mitochondrial dysfunction pathogenesis, while previously underrecognized, now more appreciated. Mitochondria are an essential organelle involved cellular bioenergetics signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, trafficking, fission, fusion dysregulated brain. Excess fission fragmentation yield mitochondria low energy production. Reduced glucose metabolism also observed hypometabolic state, particularly temporo-parietal regions. This review addresses multiple ways which abnormal structure function contribute to AD. Disruption electron transport chain ATP production neurotoxic because cells have disproportionately high demands. In addition, oxidative stress, extremely damaging nerve cells, rises dramatically dyshomeostasis. Restoring health may be viable approach treatment.

Language: Английский

Citations

27
Deciphering the Power of Resveratrol in Mitophagy: From Molecular Mechanisms to Therapeutic Applications DOI Open Access
Hongmei Liu, Yixuan Song, Huan Wang

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

Resveratrol (RES), a natural polyphenolic compound, has garnered significant attention for its therapeutic potential in various pathological conditions. This review explores how RES modulates mitophagy-the selective autophagic degradation of mitochondria essential maintaining cellular homeostasis. promotes the initiation and execution mitophagy by enhancing PINK1/Parkin-mediated mitochondrial clearance, reducing reactive oxygen species production, mitigating apoptosis, thereby preserving integrity. Additionally, regulates through activation key molecular targets such as AMP-activated protein kinase (AMPK), mechanistic target rapamycin (mTOR), deacetylases (SIRT1 SIRT3), quality control (MQC) pathways, demonstrating substantial effects multiple disease models. We provide detailed account biosynthetic pharmacokinetics, metabolic characteristics RES, focusing on role modulation implications medical applications. Potential adverse associated with clinical use are also discussed. Despite promising properties, application is limited issues bioavailability pharmacokinetic profiles. Future research should concentrate developing derivatives that precisely modulate mitophagy, unlocking new avenues therapy.

Language: Английский

Citations

3
The GLP-1 Agonist Semaglutide Ameliorates Cognitive Regression in P301S Tauopathy Mice Model via Autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization DOI
Norhan N. Elbadawy, Muhammed A. Saad, Sara Elfarrash

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177305 - 177305

Published: Jan. 1, 2025

Language: Английский

Citations

2
Updates in Alzheimer's disease: from basic research to diagnosis and therapies DOI Creative Commons

Enjie Liu,

Yao Zhang,

Jian–Zhi Wang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Sept. 4, 2024

Language: Английский

Citations

17
Modulation of cholesterol metabolism with Phytoremedies in Alzheimer’s disease: A comprehensive review DOI
Sushruta Koppula, Nitu L. Wankhede, Shivkumar S. Sammeta

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102389 - 102389

Published: June 19, 2024

Language: Английский

Citations

5
Oolong tea polyphenols affect the inflammatory response to improve cognitive function by regulating gut microbiota DOI Creative Commons

Zheyi Song,

Xin Zhang,

Mengyu Hong

et al.

Journal of Functional Foods, Journal Year: 2023, Volume and Issue: 105, P. 105584 - 105584

Published: May 19, 2023

Oolong tea polyphenols (OTP) has received increasing attention for their ability to reduce cognitive dysfunction by modulating the gut microbiota and related metabolites. In our study, circadian rhythm disorder (CRD) mice showed microbial disruption impairments. OTP treatment restored including up-regulated relative abundance of Akkermansia Muribaculum, down-regulated Desulfovibrio. Moreover, reduced inflammation response, decreased lipopolysaccharide (LPS) levels, strengthened tight junction proteins (TJPs) ameliorate intestinal barrier dysfunction. These changes inhibited elevated levels pro-inflammatory factors, therefore, attenuated neuronal damage Aβ protein aggregation in hippocampus. Additionally, supplementation also regulated metabolites function, some them closely associated with microbiota. Our findings speculate that potentially modulates impairment caused

Language: Английский

Citations

12
Harnessing Mitophagy for Therapeutic Advances in Aging and Chronic Neurodegenerative Diseases DOI Creative Commons
D. Ghosh, Alok Kumar

Neuroglia, Journal Year: 2024, Volume and Issue: 5(4), P. 391 - 409

Published: Oct. 15, 2024

Introduction: Mitophagy, the selective degradation of damaged mitochondria, is essential for maintaining cellular health and function, particularly in high-energy demanding post-mitotic cells like neurons microglial cells. Aging results impaired mitophagy, leading to mitochondrial dysfunction, oxidative stress, release damage-associated proteins (DAMPs), neuroinflammation, which contribute neurodegenerative diseases such as Alzheimer’s Parkinson’s. Mitochondrial dysfunction also contributes pathophysiology depression by affecting synaptic plasticity, increasing heightening stress. Aim: In this review, we summarize recent developments on mechanisms its therapeutic role neuroprotection, implications aging complemented future research requirements implications. Result/Discussion: Therapeutic strategies that promote health, including enhancing mitophagy biogenesis, show promise treating depression. Recent findings have emphasized modulate pharmacological agents urolithin A rapamycin, genetic interventions PINK1/Parkin gene therapy, transplantation, lifestyle dietary caloric restriction, exercise, supplements resveratrol CoQ10. Key regulators pathway various BNIP3, NIX, FUNDC1, facilitate removal play a crucial role. Conclusions: These highlight importance understanding interplay between neuroinflammation modulation can reduce stress improve neuroinflammatory outcomes age-related diseases. However, despite significant progress, challenges remain underlying molecular regulation disorders.

Language: Английский

Citations

4
Nutritional Factors: Benefits in Glaucoma and Ophthalmologic Pathologies DOI Creative Commons
Mutali Musa, Marco Zeppieri, George Nnamdi Atuanya

et al.

Life, Journal Year: 2023, Volume and Issue: 13(5), P. 1120 - 1120

Published: April 30, 2023

Glaucoma is a chronic optic neuropathy that can lead to irreversible functional and morphological damage if left untreated. The gold standard therapeutic approaches in managing patients with glaucoma limiting progression include local drops, laser, and/or surgery, which are all geared at reducing intraocular pressure (IOP). Nutrients, antioxidants, vitamins, organic compounds, micronutrients have been gaining increasing interest the past decade as integrative IOP-independent strategies delay or halt glaucomatous retinal ganglion cell degeneration. In our minireview, we examine various nutrients compounds proposed current literature for management of ophthalmology diseases, especially glaucoma. With respect each substance considered, this minireview reports molecular biological characteristics, neuroprotective activities, antioxidant properties, beneficial mechanisms, clinical studies published field general medicine. This study highlights potential benefits these substances other ophthalmologic pathologies. Nutritional supplementation thus be useful Large multicenter trials based on morphologic data collected over long follow-up periods treatments pave way alternative coadjutant options ocular

Language: Английский

Citations

11
OTULIN Interactome Reveals Immune Response and Autophagy Associated with Tauopathy in a Mouse Model DOI Creative Commons
Ling Li, Mingqi Li, Yuyang Zhou

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 8, 2025

Abstract Tauopathies are neurodegenerative diseases that pathologically characterized by accumulation of misfolded microtubule-associated protein tau aggregates in the brain. Deubiquitination, particularly OTULIN, a unique deubiquitinase targeting methionine-1 (M1) linkages from linear ubiquitin chain assembly complex (LUBAC)), is reportedly associated with neurotoxic proteins several diseases, likely including tauopathies. To investigate potential roles OTULIN tauopathies, we analyzed interactome hippocampal tissues PS19 transgenic (Tg) mice and their non-transgenic (nTg) littermate controls using affinity purification-mass spectrometry (AP-MS). We identified 705 800 enriched Tg nTg samples, respectively, false discovery rate (FDR) <1%. Of these, 189 205 were classified as probable interactors groups, based on Significance Analysis INTeractome (SAINT) score ≥0.80 FDR ≤ 5%. A total 84 group, while 100 controls. Functional enrichment analyses revealed OTULIN-interacting group pathways related to spliceosome, complement coagulation cascades, ribosome, whereas those immune response autophagy. These findings suggest may play critical role pathogenesis tauopathy this mouse model. Highlights analyzed. ribosome. implicated ATP2A2 an specifically enhanced mice.

Language: Английский

Citations

0