Exploring the Connection Between Nanomaterials and Neurodegenerative Disorders DOI Creative Commons
Sitansu Sekhar Nanda, Dong Kee Yi

Micromachines, Год журнала: 2024, Номер 15(11), С. 1382 - 1382

Опубликована: Ноя. 15, 2024

Drug delivery, tissue engineering, and cell promotion in biomedical fields heavily rely on the use of nanomaterials (NMs). When they penetrate cells, NPs undergo degradation initiate generation reactive oxygen species (ROS) by causing changes structures organelles linked to mitochondria. Inside cell, excess production ROS can a chain reaction, along with autophagy process that helps maintain balance discarding unnecessary materials. At present, there is no effective treatment for Alzheimer’s disease (AD), progressive neurodegenerative disease. The NMs siRNA delivery could become promising AD other CNS disorders. Recent research demonstrates combined induce cells. This article emphasizes importance shape siRNA-encapsulated determining their efficiency delivering suppressing gene activity central nervous system. Because its strict selectivity against foreign substances, blood–brain barrier (BBB) significantly hinders therapeutic agents brain. Conventional chemotherapeutic drugs are less brain cancers due this limitation. As result, have approach targeted drug as be modified carry specific ligands direct them intended targets. review thoroughly examines latest breakthroughs using deliver bioactive compounds across BBB, focusing cancer treatments. starts examining structure functions BBB BBTB, then benefits offer.

Язык: Английский

Tryptophan Metabolism Through the Kynurenine Pathway in Glial Cells DOI Creative Commons

Deivison Silva Argolo,

Lucas Matheus Gonçalves de Oliveira, Gilles J. Guillemin

и другие.

Neuroglia, Год журнала: 2025, Номер 6(1), С. 14 - 14

Опубликована: Март 12, 2025

The central nervous system (CNS) relies on complex and dynamic interactions between neurons glial cells. Among cells, astrocytes regulate the chemical environment surrounding supply essential nutrients for brain metabolism whereas microglia, resident macrophages of CNS, play critical roles in homeostasis, defense, responses to injury. Both microglia contribute regulation excitotoxicity inflammation mediated by tryptophan (Trp) via kynurenine pathway. Trp generates several bioactive metabolites, including quinolinic acid (QUIN) kynurenic (KYNA), which have opposing effects. QUIN, produced activated acts as an agonist NMDA receptors; excessive stimulation these receptors can lead neuronal death. Conversely, KYNA, primarily 2,3-aminotransferases (KAT), receptor antagonist, conferring neuroprotection mitigating excitotoxicity. Dysregulation is implicated many neurodegenerative diseases such Alzheimer’s disease, Parkinson’s multiple sclerosis amyotrophic lateral sclerosis, well various neuropsychiatric disorders. This review examines cellular molecular mechanisms underlying highlighting unique contributions each phenotype, implications CNS pathologies, potential biomarkers therapeutic targets restoring homeostasis preventing disease progression.

Язык: Английский

Процитировано

0
Molecular mechanism of PANoptosis and programmed cell death in neurological diseases DOI Creative Commons

Ketian Hou,

Weihong Pan,

L.-Y. Liu

и другие.

Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106907 - 106907

Опубликована: Апрель 1, 2025

PANoptosis represents a highly coordinated inflammatory programmed cell death governed by the assembly and activation of PANoptosome, which strategically integrate core molecular elements from pyroptosis, apoptosis, necroptosis. The triple-component pathways set themselves apart alternative regulated mechanisms through their unique capacity to concurrently process signals derived multiple death-signaling modalities, thereby coordinating multifaceted cellular defense system against diverse pathological insults. Pathogen-associated patterns synergistically interact with cytokine storms, oncogenic stress active PANoptosis, establishing this pathway as critical nexus in pathogenesis tumor immunomodulation. This crosstalk highlights promising therapeutic target for managing immune-related disorders malignant transformation. Emerging evidence links neuroinflammatory dysregulated between (apoptosis, necroptosis, pyroptosis) accidental necrosis, driving neuronal loss neural damage. Single-cell transcriptomics reveals spatially resolved signatures Alzheimer's hippocampal microenvironments sclerosis demyelinating plaques, distinct clusters correlating quantifiable metrics. PANoptosis-targeted therapies show preclinical promise alleviating neurovascular dysfunction while preserving physiological microglial surveillance functions. Accumulating linking (particularly PANoptosis) neurological underscores urgency deciphering its developing precision modulators next-generation therapies. review systematically deciphers PANoptosome associated cascades, evaluates roles multiscale regulatory networks, proposes frameworks advance neurology.

Язык: Английский

Процитировано

0
Advancements in Proteolysis Targeting Chimeras for Targeted Therapeutic Strategies in Alzheimer’s Disease DOI Creative Commons

Qiuzhi Zhou,

Weixia Wang, Chunchu Deng

и другие.

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Март 25, 2025

Язык: Английский

Процитировано

0
Targeting UAF1 Alleviate Neurotoxicity by Inhibiting APP/NLRP3 Axis-Mediated Pyroptosis and Apoptosis DOI Creative Commons

Ling Cheng,

Xianguang Meng,

Dandan Tian

и другие.

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Linkage of circadian rhythm disruptions with Alzheimer’s disease and therapeutic interventions DOI Creative Commons
Kishore Madhamanchi, Jianhua Zhang, Girish C. Melkani

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Combination of Epigallocatechin-3-Gallate and Tramiprosate Prevent Accumulation of Intracellular Aβ and Dysfunctional Autophagy–Lysosomal Pathway at Earliest Stage of Transdifferentiation of Mesenchymal Stromal Cells into PSEN1 E280A Cholinergic-like Neurons DOI Open Access

Viviana Soto‐Mercado,

Miguel Mendivil‐Perez, Marlene Jiménez-Del-Río

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3756 - 3756

Опубликована: Апрель 16, 2025

Familial Alzheimer’s disease (FAD) caused by presenilin 1 (PSEN1) E280A induces the aberrant accumulation of intracellular Aβ (iAβ) in cholinergic-like neurons (ChLNs). How early iAβ accumulates development ChLNs is still unknown. Consequently, timing appropriate therapeutic approaches against FAD unclear. To determine earliest PSEN1 ChLNs, flow cytometry and immunofluorescence microscopy were used to follow menstrual mesenchymal stromal cells (MenSCs) into (proliferation marker Ki67, cluster differentiation 73 (CD73), neuronal nuclei (NeuN) marker, choline acetyl transferase (ChAT)), kinetics accumulation, simultaneous evaluation other associated markers (e.g., DJ-1C106-SO3; lysosomes; phosphatidylethanolamine-conjugated microtubule-associated protein 1A/1B light chain 3, LC3-II; cleaved caspase 3 (CC3)) at 0, 1, 5, 7 days. reverse phenotype, we rapamycin (RAP), verubecestat (VER), compound E (CE), epigallocatechin-3-gallate (EGCG), tramiprosate (TM) WT mutant ChLNs. We found that did not induce significant differences NeuN ChAT MenSCs transitioning The cholinergic developmental stage from day 0 (18%, stage) (46%, stage), i.e., increased +156% compared (1–6%). A increase DJ-1C106-SO3 occurs only (+250%). While neither CC3 (0–1%) nor lysosomes different between any time point, a stepwise autophagosome was observed (15%) (79%), +427%, cells. RAP, VER, CE able completely reduce all E280A-induced combination EGCG TM more effective removing these than alone Given this investigation based on single blood sample E280A, our results should be considered exploratory. Larger sizes are needed.

Язык: Английский

Процитировано

0
Bromelain prevents Alzheimer's disease progression by suppressing oxidative stress and upregulating apolipoprotein A1 in 5x familial Alzheimer's disease transgenic mice DOI Creative Commons
Julia Chu-Ning Hsu,

Po-An Hu,

Chia‐Hui Chen

и другие.

Journal of Agriculture and Food Research, Год журнала: 2025, Номер unknown, С. 101927 - 101927

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Autophagy-lysosomal pathway impairment and cathepsin dysregulation in Alzheimer’s disease DOI Creative Commons

Alquiandra Stefani Ferreira Mançano,

João Pina,

Bruna Rojas Froes

и другие.

Frontiers in Molecular Biosciences, Год журнала: 2024, Номер 11

Опубликована: Окт. 31, 2024

Alzheimer's disease (AD) is characterized by neuronal loss, attributed to amyloid-beta (Aβ) aggregation and accumulation. The autophagy-lysosomal pathway, including cathepsins B D, crucial for protein degradation clearance, but it impaired in some diseases. This review summarizes current knowledge on the dysregulation of this pathway AD. Accumulating evidence suggests that Aβ overload impairs function cathepsin activity, exacerbating accumulation neurodegeneration. However, precise mechanisms underlying these interactions remain elusive. Despite challenges, targeting lysosomal emerges as a promising therapeutic strategy, comprehensive understanding system essential develop effective interventions

Язык: Английский

Процитировано

3
Mitostasis in age-associated neurodegeneration DOI
Mrutyunjaya Panda, Maria Markaki, Nektarios Tavernarakis

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер unknown, С. 167547 - 167547

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

1
Integrative Human Genetic and Cellular Analysis of the Pathophysiological Roles of AnxA2 in Alzheimer’s Disease DOI Creative Commons
Lianmeng Ye, Jiazheng Zhao, Zhengpan Xiao

и другие.

Antioxidants, Год журнала: 2024, Номер 13(10), С. 1274 - 1274

Опубликована: Окт. 21, 2024

Alzheimer's disease (AD) is an intractable and progressive neurodegenerative disease. Amyloid beta (Aβ) aggregation the hallmark of AD. Aβ induces neurotoxicity through a variety mechanisms, including interacting with membrane receptors to alter downstream signaling, damaging cellular or organelle membranes, interfering protein degradation synthesis, inducing excessive immune-inflammatory response, all which lead neuronal death other pathological changes associated In this study, we extracted gene expression profiles from GSE5281 GSE97760 microarray datasets in GEO (Gene Expression Omnibus) database, as well Human Gene Database. We identified differentially expressed genes brain tissues AD patients healthy persons. Through GO, KEGG, ROC analyses, annexin A2 (AnxA2) was putative target gene. Notably, accumulating evidence suggests that intracellular AnxA2 key regulator various biological processes, endocytosis, transmembrane transport, neuroinflammation, apoptosis. Thus, conducted series cell biology experiments explore function The results indicate knockdown primarily affects oxidative phosphorylation, cycle, AD, processing endoplasmic reticulum, SNARE interactions vesicular autophagy. SH-SY5Y cells secreting Aβ42, exacerbated Aβ42-induced cytotoxicity, death, ROS levels, senescence, altered reduced ATP suggesting its critical role mitochondrial maintenance. also inhibitory effect Aβ42 on migration. overexpression inflammatory response induced by while absence increased pro-inflammatory decreased anti-inflammatory responses. Furthermore, facilitated apoptosis These indicated potential pathophysiological roles

Язык: Английский

Процитировано

1