Therapeutic Transplantation of Human Central Nervous System Organoids for Neural Reconstruction DOI Open Access
Sung Jun Hong, Minsung Bock, Songzi Zhang

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8540 - 8540

Published: Aug. 5, 2024

Damage to the central nervous system (CNS) often leads irreversible neurological deficits, and there are currently few effective treatments available. However, recent advancements in regenerative medicine have identified CNS organoids as promising therapeutic options for addressing injuries. These organoids, composed of various neurons supporting cells, shown potential direct repair at injury sites. resemble structure function actual brain tissue, which allows them adapt well within physiological environment when transplanted into Research findings suggest that can replace damaged neurons, form new neural connections, promote recovery. This review highlights emerging benefits, evaluates preclinical transplantation outcomes, explores future strategies optimizing neuroregeneration using organoids. With continued research technological advancements, these could provide hope patients suffering from deficits.

Language: Английский

Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ‐on‐a‐Chip Technology DOI Creative Commons
Francesca Michela Pramotton, Sarah Spitz,

Roger D. Kamm

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(32)

Published: June 23, 2024

Abstract Neurodegenerative diseases (NDDs) affect more than 50 million people worldwide, posing a significant global health challenge as well high socioeconomic burden. With aging constituting one of the main risk factors for some NDDs such Alzheimer's disease (AD) and Parkinson's (PD), this societal toll is expected to rise considering predicted increase in population limited progress development effective therapeutics. To address failure rates clinical trials, legislative changes permitting use alternatives traditional pre‐clinical vivo models are implemented. In regard, microphysiological systems (MPS) organ‐on‐a‐chip (OoC) platforms constitute promising tool, due their ability mimic complex human‐specific tissue niches vitro. This review summarizes current modeling using OoC technology discusses five critical aspects still insufficiently addressed date. Taking these into consideration future MPS will advance vitro translational value setting.

Language: Английский

Citations

12
Limitations of human brain organoids to study neurodegenerative diseases: a manual to survive DOI Creative Commons

Nerea Urrestizala-Arenaza,

Sonia Cerchio,

Fabio Cavaliere

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 9, 2024

In 2013, M. Lancaster described the first protocol to obtain human brain organoids. These organoids, usually generated from human-induced pluripotent stem cells, can mimic three-dimensional structure of brain. While they recapitulate salient developmental stages brain, their use investigate onset and mechanisms neurodegenerative diseases still faces crucial limitations. this review, we aim highlight these limitations, which hinder organoids becoming reliable models study such as Alzheimer’s disease (AD), Parkinson’s (PD), amyotrophic lateral sclerosis (ALS). Specifically, will describe structural biological impediments, including lack an aging footprint, angiogenesis, myelination, inclusion functional immunocompetent microglia—all important factors in neurodegeneration AD, PD, ALS. Additionally, discuss technical limitations for monitoring microanatomy electrophysiology parallel, propose solutions overcome current thereby making a more tool model neurodegeneration.

Language: Английский

Citations

10
A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders DOI Creative Commons

Ana Rubio,

L. L. Hamilton,

Marcel Bausch

et al.

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 22, 2025

Most current information about neurological disorders and diseases is derived from direct patient animal studies. However, studies in many cases do not allow replication of the early stages disease and, therefore, offer limited opportunities to understand progression. On other hand, although use models allows us study mechanisms disease, they present significant limitations developing drugs for humans. Recently, 3D-cultured vitro human pluripotent stem cells have surfaced as a promising system. They potential connect findings with those models. In this comprehensive review, we discuss their application modeling neurodevelopmental conditions such Down Syndrome or Autism, neurodegenerative Alzheimer's Parkinson's, viral like Zika virus HIV. Furthermore, will different used prenatal exposure abuse, well challenges that must be met transform landscape research on brain disorders.

Language: Английский

Citations

1
Human midbrain organoids: a powerful tool for advanced Parkinson’s disease modeling and therapy exploration DOI Creative Commons
Xin Cui, Xinwei Li, Huimin Zheng

et al.

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 20, 2024

Parkinson's disease (PD) is a neurodegenerative disorder marked by the loss of dopaminergic neurons in substantia nigra. Despite progress, pathogenesis remains unclear. Human midbrain organoids (hMLOs) have emerged as promising model for studying PD, drug screening, and potential treatments. This review discusses development hMLOs, their application PD research, current challenges organoid construction, highlighting possible optimization strategies.

Language: Английский

Citations

4
Aging, cellular senescence and Parkinson's disease DOI Creative Commons
Yue Ma, Madalynn Erb, Darren J. Moore

et al.

Journal of Parkinson s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting 1–2% of people over age 65. The risk developing PD dramatically increases with advanced age, indicating that aging likely a driving factor in neuropathogenesis. Several age-associated biological changes are also hallmarks neuropathology, including mitochondrial dysfunction, oxidative stress, and neuroinflammation. Accumulation senescent cells an important feature contributes to age-related diseases. How cellular senescence affects brain health whether this phenomenon neuropathogenesis not yet fully understood. In review, we highlight aging, loss proteostasis, genomic instability telomere attrition relation well established neuropathological pathways. We then discuss context neuroscience review studies directly examine PD. Studying presents challenges holds promise for advancing our understanding mechanisms, which could contribute development effective disease-modifying therapeutics. Targeting or modulating senescence-associated secretory phenotype (SASP) requires comprehensive complex relationship between pathogenesis senescence.

Language: Английский

Citations

0
Alanine and glutathione targeting of dopamine- or ibuprofen-coupled polypeptide nanocarriers increases both crossing and protective effects on a blood–brain barrier model DOI Creative Commons
Mária Mészáros,

Thi Ha My Phan,

Judit P. Vigh

et al.

Fluids and Barriers of the CNS, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 19, 2025

Abstract Background Targeting the blood–brain barrier (BBB) is a key step for effective brain delivery of nanocarriers. We have previously discovered that combinations BBB nutrient transporter ligands alanine and glutathione (A-GSH), increase permeability vesicular polypeptide nanocarriers containing model cargo across BBB. Our aim was to investigate dopamine- ibuprofen-coupled 3-armed poly( l -glutamic acid) targeted by A-GSH transfer novel human co-culture with induced properties. In addition, protective effect ibuprofen nanoparticles on cytokine-induced damage also measured. Method Drug-coupled were synthetized characterized dynamic light scattering transmission electron microscopy. Cellular effects, uptake, investigated stem cell-based improved properties small molecular cocktail. The immunocytochemistry marker molecules. Nanocarrier uptake in endothelial cells midbrain organoids quantified spectrofluorometry visualized confocal mechanisms cellular explored addition free targeting ligands, endocytic metabolic inhibitors, co-localization intracellular organs, surface charge modification cells. against impedance measurements. Results Targeted nanoformulations both drugs showed elevated time-dependent, active manner via mechanisms. Addition inhibited internalization suggesting crucial role process. A higher measured After crossing BBB, dopamine subsequently entered midbrain-like derived from healthy Parkinson’s disease patient-specific effects damage. Conclusion BBB-targeted coupled therapeutic molecules effectively taken up or showing indicating potential applications nervous system pathologies. Graphical

Language: Английский

Citations

0
Comprehensive Review of in vitro Gut-Brain Axis Models in Parkinson’s Disease Research DOI Creative Commons
John Nicholas Cauba,

Jonathan C. G. Woo,

Robert E. Wiggins

et al.

Brain Organoid and Systems Neuroscience Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
α‐Synuclein Pathology Spreads in a Midbrain–Hindbrain Assembloid Model DOI Creative Commons
Gemma Gomez‐Giro, Daniela Frangenberg, Diana Alejandra Méndez Vega

et al.

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

Published: April 17, 2025

Understanding the progression of α-synuclein pathology in neurodegenerative diseases such as Parkinson's disease (PD) is a longstanding challenge. Here, novel midbrain-hindbrain-assembloid model that recapitulates spread observed PD patients, akin to Braak's hypothesis, presented. Initially, presence demonstrated hindbrain organoids. Subsequently, sophisticated tissue engineering methods are employed create midbrain-hindbrain assembloids. These assembloids allow investigation and description spreading pathology, it progresses from components midbrain regions within integrated structure. It an increase can induce transfer into healthy midbrain, well cause changes at synapse level. The presented constitutes robust vitro platform for investigating mechanisms underlying progression, holding potential screening prospective therapeutics targeting pathological propagation related synucleinopathies.

Language: Английский

Citations

0
Genetic study of the NUS1 gene variants in Han Chinese patients with Parkinson’s disease DOI Open Access

Cui Gao,

Lamei Yuan, Wen Zheng

et al.

Ageing and Neurodegenerative Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Aim: Parkinson’s disease (PD) is the second most common progressive neurodegenerative linked to genetic and other factors. The NUS1 dehydrodolichyl diphosphate synthase subunit gene (NUS1) variants were reported be associated with PD. In this PD-control cohort, we aimed explore potential role of in Methods: A cohort 512 Han Chinese sporadic PD patients 516 ethnically age-matched controls underwent clinical evaluation. Peripheral blood samples then collected, whole-exome sequencing was performed. PD-related identified through screening verified using Sanger sequencing, further classified, subsequently analyzed by bioinformatics analysis tools. Statistical conducted assess association between Results: Three heterozygous missense variants, including c.127G>T (p.Ala43Ser, rs1327892878), c.487G>C (p.Asp163His, rs369403261), c.537T>A (p.Asp179Glu, rs28362519), identified. Two rare c.487G>C, exclusively found patients, while low-frequency variant detected both controls. Combined analysis, a potentially pathogenic may exert risk, though no significant shown statistical (all P > 0.05). Conclusion: Our findings suggested that seem not cause monogenic PD, like may, at most, susceptibility

Language: Английский

Citations

0
Experimental Cell Models for Investigating Neurodegenerative Diseases DOI Open Access
Cecilia Evangelisti, Sherin Ramadan, Antonio Orlacchio

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9747 - 9747

Published: Sept. 9, 2024

Experimental models play a pivotal role in biomedical research, facilitating the understanding of disease mechanisms and development novel therapeutics. This is particularly true for neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis, motor neuron which present complex challenges research therapy development. In this work, we review recent literature about experimental disease. We identified three main categories that are highly studied by scientists. fact, investigating these diseases encompass variety approaches, including modeling patient’s cell culture, patient-derived induced pluripotent stem cells, organoids. Each model offers unique advantages limitations, providing researchers with range tools to address biological questions. Here, discuss characteristics, applications, advancements terms each system, highlighting their contributions advancing knowledge translational research.

Language: Английский

Citations

3