Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Male Mice DOI Creative Commons

Wei-li Chang,

Karly Tegang,

Benjamin A. Samuels

et al.

Biological Psychiatry Global Open Science, Journal Year: 2024, Volume and Issue: 5(2), P. 100419 - 100419

Published: Nov. 20, 2024

Impairments in behavioral pattern separation (BPS)-the ability to distinguish between similar contexts or experiences-contribute memory interference and overgeneralization seen many neuropsychiatric conditions, including depression, anxiety, posttraumatic stress disorder, dementia, age-related cognitive decline. Although BPS relies on the dentate gyrus is sensitive changes adult hippocampal neurogenesis, its significance as a pharmacological target has not been tested. In this study, we applied human neural stem cell high-throughput screening cascade identify compounds that increase neurogenesis. One compound with favorable profile, RO6871135, was then tested young aged mice for effects anxiety-related behaviors. Chronic treatment RO6871135 (7.5 mg/kg) increased neurogenesis improved fear discrimination task both mice. also lowered innate anxiety-like behavior, which more apparent exposed chronic corticosterone. Ablation of by irradiation supported neurogenesis-dependent mechanism RO6871135-induced improvements BPS. To possible mechanisms action, vitro vivo kinase inhibition chemical proteomics assays were performed. These tests indicated inhibited CDK8, CDK11, CaMKIIa, CaMKIIb, MAP2K6, GSK-3β. An analog demonstrated high affinity studies demonstrate method empirical identification preclinical testing novel neurogenic can improve point be interrogated development new therapies specific endophenotypes such impaired

Language: Английский

PI3K/AKT signaling pathway: Molecular mechanisms and therapeutic potential in depression DOI Creative Commons
Ningning Guo, Xin Wang,

Muran Xu

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 206, P. 107300 - 107300

Published: July 9, 2024

Depression is a serious global mental disorder. Numerous studies have found that depression may be closely related to decreased neurogenesis, neuroinflammation, neurotransmitter imbalance, and synaptic plasticity dysfunction. The pathogenesis of complex involves multiple signal transduction pathways molecular changes. PI3K/AKT pathway an essential signaling in neurons, which widely expressed emotion-related regions the brain. Therefore, play moderating role mood disorders. However, mechanism not been fully described. This review systematically summarized discussed its potential treatment depression. will help development antidepressants.

Language: Английский

Citations

25
Decoding the Role of Neurotrophins in Glycogen Synthase Kinase 3-Beta Regulation in Alzheimer’s Disease DOI

Shubham Nilkanth Rahmatkar,

Damanpreet Singh

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

Citations

1
Friend or foe: Lactate in neurodegenerative diseases DOI
Mingyu Wang, Yang Zhou,

Wenlian Li

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 101, P. 102452 - 102452

Published: Aug. 8, 2024

Language: Английский

Citations

8
Unlocking Hope: Therapeutic Advances and Approaches in Modulating the Wnt Pathway for Neurodegenerative Diseases DOI Creative Commons

Navid Faraji,

Negar Ebadpour, Mohammad Abavisani

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 23, 2024

Language: Английский

Citations

5
Enhancing proteasome activity by NMDAR antagonists explains their therapeutic effect in neurodegenerative and mental diseases DOI Creative Commons
Fikret Şahin, Aslıhan Günel, Buse Türegün Atasoy

et al.

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

Published: Jan. 13, 2025

NMDAR antagonists, such as memantine and ketamine, have shown efficacy in treating neurodegenerative diseases major depression. The mechanism by which these drugs correct the aforementioned is still unknown. Our study reveals that antagonists significantly enhance 20S proteasome activity, crucial for degrading intrinsically disordered, oxidatively damaged, or misfolded proteins, factors pivotal like Alzheimer's Parkinson's. In our mouse model experiment, ketamine administration notably altered brain synaptic protein profiles within two hours, downregulating proteins strongly associated with Parkinson's diseases. Furthermore, exhibited enrichment terms related to plasticity potentiation, including retrograde endocannabinoid signaling—a pathway both short- long-term may elucidate long-lasting effects of Via ubiquitin-independent (UIPS), maintain cellular homeostasis, activity declines age, leading aggregation disease symptoms. Therefore, findings hold promise new treatment options not only but also other systemic conditions unfolded proteins.

Language: Английский

Citations

0
Antioxidant, Osteogenic, and Neuroprotective Effects of Homotaurine in Aging and Parkinson’s Disease Models DOI Creative Commons
Arianna Minoia,

Francesca Cristiana Piritore,

Silvia Bolognin

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 249 - 249

Published: Feb. 21, 2025

Aging is associated with the accumulation of cellular damage due to oxidative stress and chronic low-grade inflammation, collectively referred as "inflammaging". This contributes functional decline in various tissues, including brain skeletal system, which closely interplay. Mesenchymal stem cells (MSCs), known for their regenerative potential ability modulate offer a promising therapeutic approach counteract aging-related declines. In this study, we investigated effects homotaurine (a small molecule neuroprotective properties) on MSCs its osteogenesis. We found that treatment significantly reduced reactive oxygen species (ROS) levels, improved MSC viability, modulated key response pathways, sestrin 1 p21 proteins. Furthermore, promoted osteogenesis angiogenesis zebrafish models by enhancing expression critical osteogenesis-associated genes, such those coding β-catenin Runt-related transcription factor 2 (Runx2), increasing levels kinase insert domain receptor-like marker aged zebrafish. Parkinson's disease using patient-specific midbrain organoids leucine-rich repeat G2019S mutation, enhanced ROS highlighting dysfunctional signaling pathways neurodegeneration. Our findings suggest not only offers benefits but also holds promise dual-target strategy both neuronal bone homeostasis aging neurodegenerative diseases.

Language: Английский

Citations

0
Role of an interdependent Wnt, GSK3-β/β-catenin and HB-EGF/EGFR mechanism in arsenic-induced hippocampal neurotoxicity in adult mice DOI

Asmita Garg,

Sanghamitra Bandyopadhyay

Chemosphere, Journal Year: 2024, Volume and Issue: 352, P. 141375 - 141375

Published: Feb. 5, 2024

Language: Английский

Citations

3
Decoding multiple sclerosis: Unravelling the complexities of pathogenesis, progression, mechanisms and therapeutic innovations DOI

Syeda Rida Zainab,

Jehanzeb Khan, Muhammad Khalid Tipu

et al.

Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

3
Polyphenols as Wnt/β‐catenin pathway modulators: A promising strategy in clinical neurodegeneration DOI Creative Commons

Biswajit Kumar Utpal,

Soma Roy, Mehrukh Zehravi

et al.

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Polyphenols, a diverse group of naturally occurring compounds found in plants, have garnered significant attention for their potential therapeutic properties treating neurodegenerative diseases (NDs). The Wnt/β-catenin (WβC) signaling pathway, crucial player neurogenesis, neuronal survival, and synaptic plasticity, is involved several cellular mechanisms related to NDs. Dysregulation this pathway hallmark the development various This study explores multiple polyphenolic compounds, such as flavonoids, stilbenes, lignans, phenolic acids, protect nervous system. It provides comprehensive analysis effects on WβC elucidating modes action. highlights dual function polyphenols regulating protecting system, providing reassurance about research benefits. review results obtained from both vitro studies vivo research, shedding light how these substances influence components pathway. focus mainly molecular that allow reduce oxidative stress, inflammation, apoptotic processes, ultimately improving survival neurons. aims offer thorough understanding targeting which could lead innovative options

Language: Английский

Citations

0
Investigating the Expression Pattern, Prognostic and Immunological Significance of the WNT family in Breast Cancer DOI Creative Commons

Fatema Tuj Johora Fariha,

Muztaba Fuad, Chandan Saha

et al.

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

Published: Feb. 14, 2025

Abstract Breast cancer (BRCA) is one of the most diagnosed cancers and leading cause cancer-related deaths among women globally. Previous studies have shown that WNT (wingless type) family plays a role in development various cancers. However, comprehensive analysis WNTs BRCA remains largely unexplored. In this extensive study, we examined expression patterns, clinical relevance, survival outcomes associated with identified key prognostic WNTs. We further investigated genetic alterations, DNA methylation, drug sensitivity using cBioPortal, SMART, GSCA databases. Data from GEO DepMap were used for validation. Our findings revealed WNT2 WNT7B significantly upregulated, while WNT11 was downregulated, which affected overall patients BRCA. Amplification common type alteration selected analysis, showing significant correlation immune cells therapy-related genes. Enrichment involvement crucial pathways responsible cancer. Additionally, their co-expressed genes strongly efficacy anticancer drugs. This study highlights dysregulation progression patient survival, suggesting potential immunotherapeutic target valuable biomarker management treatment.

Language: Английский

Citations

0