Cell, Journal Year: 2024, Volume and Issue: 187(17), P. 4690 - 4712.e30
Published: Aug. 1, 2024
Language: Английский
Aging and Disease, Journal Year: 2023, Volume and Issue: unknown
Published: Aug. 8, 2023
Alzheimer's disease (AD) is a prevalent neurodegenerative characterized by both amnestic and non-amnestic clinical manifestations. It accounts for approximately 60-70% of all dementia cases worldwide. With the increasing number AD patients, elucidating underlying mechanisms developing corresponding interventional strategies are necessary. Hypotheses about such as amyloid cascade, Tau hyper-phosphorylation, neuroinflammation, oxidative stress, mitochondrial dysfunction, cholinergic, vascular hypotheses not mutually exclusive, them play certain role in development AD. The cascade hypothesis currently most widely studied; however, other also gaining support. This article summarizes recent evidence regarding major pathological their potential interplay, well strengths weaknesses each implications effective treatments. could stimulate further studies promote more therapeutic
Language: Английский
Citations
66
Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 511 - 511
Published: March 14, 2024
Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s (PD), traumatic brain injury (TBI) Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions these pathogeneses is currently not clearly understood. These show dysregulated inflammatory responses, activation neurons, glial cells, neurovascular unit damage associated with excessive release proinflammatory cytokines, chemokines, neurotoxic mediators, infiltration peripheral immune cells into brain, as well entry mediators through damaged endothelial blood–brain barrier tight junction proteins. Activation leads to many molecules that cause neuroinflammation neurodegeneration. Gulf War Illness (GWI) myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) also dysfunctions. Currently, there no effective disease-modifying therapeutic options available for diseases. Human induced pluripotent stem cell (iPSC)-derived astrocytes, microglia, pericytes used models drug discovery. This review highlights certain recent trends in neuroinflammatory responses iPSC-derived applications
Language: Английский
Citations
30
Biomolecules, Journal Year: 2023, Volume and Issue: 13(2), P. 313 - 313
Published: Feb. 7, 2023
The deposition of amyloid-beta (Aβ) plaques in the brain is one primary pathological characteristics Alzheimer’s disease (AD). It can take place 20–30 years before onset clinical symptoms. imbalance between production and clearance Aβ major causes AD. Enhancing at an early stage attractive preventive therapeutic strategy Direct inhibition aggregation using small molecules, peptides, monoclonal antibody drugs has not yielded satisfactory efficacy trials for decades. Novel approaches are required to understand combat deposition. Neurological dysfunction a complex process that integrates functions different types cells brain. role non-neurons AD been fully elucidated. An in-depth understanding interactions neurons contribute elucidation formation identification effective drug targets. patient-derived pluripotent stem (PSCs) contain complete background information have potential differentiate into various vitro, which may bring new insight treatment Here, we systematically review latest studies on clarify roles cell among microglia, astroglia response plaques, will be beneficial explore methods reconstructing models inducible PSCs (iPSCs) through differentiation techniques validating applications plaques. This provide most promising directions finding clues preventing delaying development
Language: Английский
Citations
28
Stem Cell Reviews and Reports, Journal Year: 2024, Volume and Issue: 20(6), P. 1375 - 1386
Published: April 19, 2024
Various groups including animal protection organizations, medical research centers, and even federal agencies such as the U.S. Food Drug Administration, are working to minimize use in scientific experiments. This movement primarily stems from welfare ethical concerns. However, recent advances technology new studies medicine have contributed an increase experiments throughout years. With rapid testing, concerns arise issues, high cost, complex procedures, potential inaccuracies.Alternative solutions recently been investigated address problems of testing. Some these technologies related stem cell technologies, organ-on-a-chip, organoids, induced pluripotent models. The aim review is focus on methodologies, that can serve alternative testing discuss its advantages limitations, alongside regulatory considerations.Although methodologies has shortcomings, it replace Achieving this requires further cells, with societal technological benefits.
Language: Английский
Citations
15
The Neuroscientist, Journal Year: 2025, Volume and Issue: unknown
Published: March 13, 2025
Harnessing intelligence from brain cells in vitro requires a multidisciplinary approach integrating wetware, hardware, and software. Wetware comprises the themselves, where differentiation induced pluripotent stem offers ethical scalability; hardware typically involves life support system setup to record activity deliver stimulation cells; software is required control process signals coming going cells. This review provides broad summary of foundational technologies underpinning these components, along with outlining importance technology integration. Of particular that this new ability extend beyond traditional methods assess primarily survival spontaneous neural cultures. Instead, focus returns core function tissue: neurocomputational information respond accordingly. Therefore, also covers work that, despite relatively early state current technology, has provided novel meaningful understandings field neuroscience opening exciting avenues for future research.
Language: Английский
Citations
1
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
Cell Reports, Journal Year: 2023, Volume and Issue: 42(11), P. 113310 - 113310
Published: Oct. 20, 2023
During the past two decades, induced pluripotent stem cells (iPSCs) have been widely used to study human neural development and disease. Especially in field of Alzheimer's disease (AD), remarkable effort has put into investigating molecular mechanisms behind this Then, with advent 3D neuronal cultures cerebral organoids (COs), several studies demonstrated that model can adequately mimic familial sporadic AD. Therefore, we created an AD-CO using iPSCs derived from patients AD forms explored early events progression pathogenesis. Our COs three AD-iPSC lines PSEN1(A246E) or PSEN2(N141I) mutations developed AD-specific markers vitro, yet they also uncover tissue patterning defects altered development. These findings are complemented by single-cell sequencing data confirming observation uncovering neurons AD-COs likely differentiate prematurely.
Language: Английский
Citations
16
Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17
Published: June 9, 2023
Hypoxic-ischemic encephalopathy (HIE) is the leading cause of long-term neurological disability in neonates and adults. Through bibliometric analysis, we analyzed current research on HIE various countries, institutions, authors. At same time, extensively summarized animal models modeling methods. There are opinions neuroprotective treatment HIE, main therapy clinical therapeutic hypothermia, although its efficacy remains to be investigated. Therefore, this study, discussed progress neural circuits, injured brain tissue, circuits-related technologies, providing new ideas for prognosis management with combination neuroendocrine neuroprotection.
Language: Английский
Citations
14
Biomedicines, Journal Year: 2023, Volume and Issue: 11(5), P. 1261 - 1261
Published: April 24, 2023
Sex differences are present in brain morphology, sex hormones, aging processes and immune responses. These need to be considered for proper modelling of neurological diseases with clear differences. This is the case Alzheimer’s disease (AD), a fatal neurodegenerative disorder two-thirds cases diagnosed women. It becoming that there complex interplay between system, hormones AD. Microglia major players neuroinflammatory process occurring AD have been shown directly affected by hormones. However, many unanswered questions remain as importance including both sexes research studies has only recently started receiving attention. In this review, we provide summary their implications AD, focus on microglia action. Furthermore, discuss current available study models, emerging microfluidic 3D cellular models usefulness studying hormonal effects disease.
Language: Английский
Citations
12
Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)
Published: Oct. 25, 2023
Cholesterol is important for membrane integrity and cell signaling, dysregulation of the distribution cellular cholesterol associated with numerous diseases, including neurodegenerative disorders. While regulated transport a specific pool cholesterol, known as "accessible cholesterol", contributes to maintenance homeostasis, tools monitor accessible in live cells remain limited. Here, we engineer highly sensitive biosensor by taking advantage cholesterol-sensing element (the GRAM domain) an evolutionarily conserved lipid transfer protein, GRAMD1b. Using this biosensor, which call GRAM-W, successfully visualize real time many different types, human keratinocytes iPSC-derived neurons, show differential dependencies on biosynthesis uptake maintaining levels cholesterol. Furthermore, combine GRAM-W dimerization-dependent fluorescent protein (ddFP) establish strategy ultrasensitive detection plasma These will allow us obtain insights into molecular mechanisms regulated.
Language: Английский
Citations
12