Postsynaptic lncRNA Sera/Pkm2 pathway orchestrates the transition from social competition to rank by remodeling the neural ensemble in mPFC DOI Creative Commons
Ling‐Shuang Zhu,

Chuan Lai,

Chao-Wen Zhou

et al.

Cell Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Aug. 20, 2024

Individuals' continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both competition and However, molecular regulatory mechanisms underlying neural ensemble mPFC remains unclear. Here, we demonstrate that excitatory neurons of prelimbic (PL), lncRNA Sera remodels utilization Pkm Exon9 Exon10, resulting a decrease Pkm1/2 ratio highly mice. By employing tet-on/off system, disrupt or rebuild normal by controlling expression Pkm2 PL neurons. We find long-term modulation induces timely alteration hysteretic rank change, through phosphorylating Ser845 site GluA1. Together, this study uncovers crucial role Sera/Pkm2 pathway transition to remodeling mPFC.

Language: Английский

The interaction of lipocalin-2 and astrocytes in neuroinflammation: mechanisms and therapeutic application DOI Creative Commons
Qianqian Tan, Chenxi Zhang, Xiuqin Rao

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: March 12, 2024

Neuroinflammation is a common pathological process in various neurological disorders, including stroke, Alzheimer’s disease, Parkinson’s and others. It involves the activation of glial cells, particularly astrocytes, release inflammatory mediators. Lipocalin-2 (Lcn-2) secretory protein mainly secreted by activated which can affect neuroinflammation through pathways. also act as pro-inflammatory factor modulating astrocyte polarization different signaling pathways, such NF-κB, JAK-STAT, amplifying response aggravating neural injury. Consequently, Lcn-2 astrocytes may be potential therapeutic targets for related diseases. This review summarizes current knowledge on role mechanisms, interactions, implications neuroinflammation.

Language: Английский

Citations

9
Genetically Programmed Single‐Component Protein Hydrogel for Spinal Cord Injury Repair DOI Creative Commons
Wei Yi, Xiaolin Zhou, Zhenhua Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Protein self‐assembly allows for the formation of diverse supramolecular materials from relatively simple building blocks. In this study, a single‐component self‐assembling hydrogel is developed using recombinant protein CsgA, and its successful application spinal cord injury repair demonstrated. Gelation achieved by physical entanglement CsgA nanofibrils, resulting in self‐supporting at low concentrations (≥5 mg mL −1 ). By leveraging programmability gene sequence, bioactive enhanced fusing functional peptide GHK. GHK recognized anti‐inflammatory, antioxidant, neurotrophic factor‐stimulating properties, making it valuable addition to applications. vitro experiments demonstrate that CsgA‐GHK can modulate microglial M2 polarization, promote neuronal differentiation neural stem cells, inhibit astrocyte differentiation. Additionally, shows efficacy alleviating inflammation promotes regeneration site, leading significant recovery rat model with compression cavity. These findings lay groundwork developing modular design platform hydrogels tissue

Language: Английский

Citations

1
Unlocking the Epigenetic Symphony: Histone Acetylation’s Impact on Neurobehavioral Change in Neurodegenerative Disorders DOI
Balapal S. Basavarajappa, Shivakumar Subbanna

Epigenomics, Journal Year: 2024, Volume and Issue: 16(5), P. 331 - 358

Published: Feb. 7, 2024

Recent genomics and epigenetic advances have empowered the exploration of DNA/RNA methylation histone modifications crucial for gene expression in response to stress, aging disease. Interest understanding neuronal plasticity's mechanisms, influencing brain rewiring amid development, neurodegenerative disorders, continues grow. Histone acetylation dysregulation, a commonality diverse has become therapeutic focus. acetyltransferases deacetylases emerged as promising targets disorder treatment. This review delves into regulation, potential therapies future perspectives disorders like Alzheimer's, Parkinson's Huntington's. Exploring genetic-environmental interplay through models studies reveals molecular changes, behavioral insights early intervention possibilities targeting epigenome at-risk individuals.

Language: Английский

Citations

8
Recognizing Alzheimer's disease from perspective of oligodendrocytes: Phenomena or pathogenesis? DOI Creative Commons
Jingji Wang, Yilan Zhen,

Jun Yang

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Abstract Background Accumulation of amyloid beta, tau hyperphosphorylation, and microglia activation are the three highly acknowledged pathological factors Alzheimer's disease (AD). However, oligodendrocytes (OLs) were also widely investigated in pathogenesis treatment for AD. Aims We aimed to update regulatory targets differentiation maturation OLs, emphasized key role OLs occurrence Methods This review first concluded OL with AD pathogenesis, then advanced based on both clinic basic experiments. Later, we extensively discussed possible application current progress diagnosis this complex disease. Results Molecules involving OLs’ or maturation, including various transcriptional factors, cholesterol homeostasis regulators, microRNAs could participate Clinical data point towards impairment patients. Basic research further supports central regulation pathologies. Additionally, classic drugs, donepezil, edaravone, fluoxetine, clemastine demonstrate their potential remedying models, new therapeutics from perspective is constantly being developed. Conclusions believe that dysfunction one important Factors regulating might be biomarkers early agents stimulating warrant development anti‐AD drugs.

Language: Английский

Citations

7
Curcumin as a potential therapeutic agent for treating neurodegenerative diseases DOI Creative Commons

Valeria Perales-Salinas,

Sushmitha S. Purushotham,

Yossi Buskila

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 178, P. 105790 - 105790

Published: June 7, 2024

Neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function, posing a tremendous burden on health systems worldwide. Although underlying pathological mechanisms for various neurodegenerative still unclear, common hallmark is abundance neuroinflammatory processes, which affect both disease onset progression. In this review, we explore pathways role neuroinflammation in further assess potential use curcumin, natural spice with antioxidant anti-inflammatory properties that has been extensively used worldwide as traditional medicine therapeutic agent. Following examination preclinical clinical studies assessed curcumin agent, highlight bioavailability body discuss challenges benefits using compound treating neurodegeneration. elucidating involvement aging neurodegeneration great developing future CNS-related targets, research required to elucidate Curcumin affects brain physiology, especially BBB integrity, under physiological conditions.

Language: Английский

Citations

7
Induced Pluripotent Stem Cells and Organoids in Advancing Neuropathology Research and Therapies DOI Creative Commons

Douglas Bottega Pazzin,

Thales Thor Ramos Previato, João Ismael Budelon Gonçalves

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(9), P. 745 - 745

Published: April 25, 2024

This review delves into the groundbreaking impact of induced pluripotent stem cells (iPSCs) and three-dimensional organoid models in propelling forward neuropathology research. With a focus on neurodegenerative diseases, neuromotor disorders, related conditions, iPSCs provide platform for personalized disease modeling, holding significant potential regenerative therapy drug discovery. The adaptability iPSCs, along with associated methodologies, enables generation various types neural cell differentiations their integration models, effectively replicating complex tissue structures vitro. Key advancements iPSC protocols, alongside careful selection donor types, are emphasized as critical steps harnessing these technologies to mitigate tumorigenic risks other hurdles. Encouragingly, show promising outcomes therapies, evidenced by successful application animal models.

Language: Английский

Citations

6
A comprehensive study on epigenetic biomarkers in early detection and prognosis of Alzheimer's disease DOI Creative Commons
Dhruv Parikh, Manan Shah

Deleted Journal, Journal Year: 2024, Volume and Issue: 1(2), P. 138 - 153

Published: June 1, 2024

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques and tau tangles, disrupting brain cell communication, causing atrophy, leading to cognitive decline. It poses substantial global health challenge, necessitating urgent research. Molecular biomarkers, reflecting AD progression, have been identified in diverse bodily tissues. Notably, emerging epigenetic biomarkers introduce novel dimension pathophysiology. However, their precise role early detection prognosis remains unclear. This review classifies various emphasizing potential prognosis. Various like DNA methylation, non-coding RNAs, histone modification, OMICS, many more get significantly altered during AD; these being distinctly expressed normal conditions offer huge therapeutic benefit stop the progression or worsening it. We explore implications propose integration with existing diagnostic methods intervene mitigating exacerbation. Addressing challenges, we envision future scope of synergy computational approaches for enhanced detection. contributes field proposing multifaceted approach that combines markers analysis improve facilitate timely interventions. Furthermore, discuss economic application could reduce financial burden delaying severity disease.

Language: Английский

Citations

5
Diagnostic and mechanistic roles of MicroRNAs in neurodevelopmental & neurodegenerative disorders DOI Creative Commons
Mohamed Adil Shah Khoodoruth,

Widaad Nuzhah Chut‐kai Khoodoruth,

Maira Uroos

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: unknown, P. 106717 - 106717

Published: Oct. 1, 2024

Language: Английский

Citations

4
Cpeb1 remodels cell type–specific translational program to promote fear extinction DOI Creative Commons

Juan Zhang,

Chunqing Yang,

Zhiqiang Liu

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(2)

Published: Jan. 10, 2025

Protein translation is crucial for fear extinction, a process vital adaptive behavior and mental health, yet the underlying cell-specific mechanisms remain elusive. Using Tet-On 3G genetic approach, we achieved precise temporal control over protein in infralimbic medial prefrontal cortex ( IL ) during extinction. In addition, our results reveal that disruption of cytoplasmic polyadenylation element binding 1 (Cpeb1) leads to notable alterations cell type–specific translational programs, thereby affecting Specifically, Cpeb1 deficiency neurons activates heterochromatin 3, which enhances microRNA networks, whereas microglia, it suppresses chemokine receptor Cx3cr1 ), resulting an aged-like microglial phenotype. These coordinated impair spine formation plasticity. Our study highlights critical role extinction provides insight into therapeutic targets disorders with deficits.

Language: Английский

Citations

0
GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau DOI Creative Commons

Diana Acosta Ingram,

Emir Turkes, Tae Yeon Kim

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 9, 2025

Lipid dyshomeostasis and tau pathology are present in frontotemporal lobar degeneration (FTLD) Alzheimer's disease (AD). However, the relationship between lipid remains unclear. We report that GRAM Domain Containing 1B (GRAMD1B), a nonvesicular cholesterol transporter, is increased excitatory neurons of human neural organoids (HNOs) with MAPT R406W mutation. Human FTLD, AD cases, PS19 mice also have GRAMD1B expression. show overexpression increases levels free cholesterol, droplets, impairs autophagy flux. Modulating iPSC-derived alters key autophagy-related components such as PI3K, phospho-AKT, p62, well phosphorylated tau, CDK5R1. Blocking function decreases droplets. Knocking down additionally reduces CDK5R1 Our findings elucidate role nervous system highlight its relevance to FTLD AD.

Language: Английский

Citations

0