Optogenetic induction of alpha-synuclein aggregation in human dopaminergic neurons to model Parkinson’s disease pathology DOI Creative Commons

Eun A.,

Min Seong Kim,

Gabsang Lee

et al.

STAR Protocols, Journal Year: 2023, Volume and Issue: 4(4), P. 102609 - 102609

Published: Sept. 23, 2023

Alpha-synuclein (α-syn) aggregation is a principal factor in Parkinson's disease (PD) onset. Here, we present protocol for optogenetic induction of α-syn human midbrain dopaminergic (mDA) neurons, facilitating detailed PD pathology study. We describe steps nucleofection the opto-α-syn construct, single colony selection and validation, alongside mDA neuron differentiation rapid toxic aggregates via blue light. This establishes potent induced pluripotent-stem-cell-based platform drug testing validation. For complete details on use execution this protocol, please refer to Kim et al. (2023).1

Language: Английский

Lighting the way: recent developments and applications in molecular optogenetics DOI Creative Commons

Anja Armbruster,

Asim ME Mohamed, Hoang Trong Phan

et al.

Current Opinion in Biotechnology, Journal Year: 2024, Volume and Issue: 87, P. 103126 - 103126

Published: March 29, 2024

Molecular optogenetics utilizes genetically encoded, light-responsive protein switches to control the function of molecular processes. Over last two years, there have been notable advances in development novel optogenetic switches, their utilization elucidating intricate signaling pathways, and progress toward practical applications biotechnological processes, material sciences, therapeutic applications. In this review, we discuss these areas, offer insights into recent developments, contemplate future directions.

Language: Английский

Citations

9

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

9

Clinical, mechanistic, biomarker, and therapeutic advances in GBA1-associated Parkinson’s disease DOI Creative Commons
Xuxiang Zhang,

Heng Wu,

Beisha Tang

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Sept. 12, 2024

Language: Английский

Citations

9

Protein Design Accelerates the Development and Application of Optogenetic Tools DOI Creative Commons

Lingyun Zhu,

Yuxuan Wang, Xiaomin Wu

et al.

Computational and Structural Biotechnology Journal, Journal Year: 2025, Volume and Issue: 27, P. 717 - 732

Published: Jan. 1, 2025

Optogenetics has substantially enhanced our understanding of biological processes by enabling high-precision tracking and manipulation individual cells. It relies on photosensitive proteins to monitor control cellular activities, thereby paving the way for significant advancements in complex system research. Photosensitive play a vital role development optogenetics, facilitating establishment cutting-edge methods. Recent breakthroughs protein design have opened up opportunities develop protein-based tools that can precisely manipulate activities. These will significantly accelerate application optogenetic tools. This article emphasizes pivotal tools, offering insights into potential future directions. We begin providing an introduction historical fundamental principles followed exploration operational mechanisms key domains, which includes clarifying conformational changes they undergo response light, such as allosteric modulation dimerization processes. Building this foundation, we reveal enable creation even more sophisticated techniques.

Language: Английский

Citations

1

Advances in animal models of Parkinson's disease DOI Creative Commons

He Sui,

Qin Ru, Lin Chen

et al.

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 215, P. 111024 - 111024

Published: July 4, 2024

Parkinson's disease is a complex neurodegenerative characterized by progressive movement impairments. Predominant symptoms encompass resting tremor, bradykinesia, limb rigidity, and postural instability. In addition, it also includes series of non-motor such as sleep disorders, hyposmia, gastrointestinal dysfunction, autonomic dysfunction cognitive impairment. Pathologically, the manifests through dopaminergic neuronal loss presence Lewy bodies. At present, no significant breakthrough has been achieved in clinical treatment. Exploring treatment modalities necessitate establishment scientifically sound animal models. recent years, researchers have focused on replicating human disease, resulting various experimental models primarily drugs transgenic methods to mimic relevant pathologies identify more effective treatments. This review examines traditional neurotoxin well α-synuclein pre-formed fibrils models, non-human primate non-mammalian specie Additionally, introduces emerging including based optogenetics, induced pluripotent stem cells, gene editing, aiming provide reference for utilization research this field.

Language: Английский

Citations

7

Precision Medicine in Parkinson's Disease Using Induced Pluripotent Stem Cells DOI

Min Seong Kim,

Hyesoo Kim, Gabsang Lee

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(21)

Published: Jan. 25, 2024

Parkinson's disease (PD) is one of the most devastating neurological diseases; however, there no effective cure yet. The availability human induced pluripotent stem cells (iPSCs) provides unprecedented opportunities to understand pathogenic mechanism and identification new therapy for PD. Here a model system PD, including 2D iPSC-derived midbrain dopaminergic (mDA) neurons, 3D organoids (MOs) with cellular complexity, more advanced microphysiological systems (MPS) organoids, introduced. It believed that successful integrations applications iPSC, organoid, MPS technologies can bring insight on PD's pathogenesis will lead treatments this debilitating disease.

Language: Английский

Citations

5

Application Prospect of Induced Pluripotent Stem Cells in Organoids and Cell Therapy DOI Open Access
Teng Zhang, Cheng Qian,

Mengyao Song

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(5), P. 2680 - 2680

Published: Feb. 26, 2024

Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based modeling assessment primarily operated at the cellular level, recent years have witnessed significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling observation of progression metabolism an vivo-like environment, surpassing capabilities iPSC-derived cells. Furthermore, therapy emerged focal point clinical interest. In this review, we provide extensive overview non-integrative reprogramming methods that evolved since inception iPSC technology. We also deliver comprehensive examination organoids, spanning realms nervous system, cardiovascular oncology, well systematically elucidate advancements iPSC-related therapies.

Language: Английский

Citations

5

Engineering organoids as cerebral disease models DOI Creative Commons
Alexander Geidies,

Marija Lj Medar,

Hannes M. Beyer

et al.

Current Opinion in Biotechnology, Journal Year: 2025, Volume and Issue: 92, P. 103253 - 103253

Published: Jan. 14, 2025

Cerebral organoids pioneered in replicating complex brain tissue architectures vitro, offering a vast potential for human disease modeling. They enable the vitro study of physiological and pathophysiological mechanisms various neurological diseases disorders. The trajectory technological advancements organoid generation engineering over past decade indicates that technology might, future, mature into indispensable solutions at horizon personalized regenerative medicine. In this review, we highlight recent advances as models discuss some challenges opportunities future research rapidly evolving field.

Language: Английский

Citations

0

Age-Related Neurodegenerative Diseases: A Stem Cell’s Perspective DOI Creative Commons
Belén Calvo, Pierre Schembri-Wismayer, María Beatriz Durán Alonso

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 347 - 347

Published: Feb. 27, 2025

Neurodegenerative diseases encompass a number of very heterogeneous disorders, primarily characterized by neuronal loss and concomitant decline in neurological function. Examples this type clinical condition are Alzheimer's Disease, Parkinson's Huntington's Disease Amyotrophic Lateral Sclerosis. Age has been identified as major risk the etiology these which explains their increased incidence developed countries. Unfortunately, despite continued intensive efforts, no cure yet found for any diseases; reliable markers that allow an early diagnosis disease identification key molecular events leading to onset progression lacking. Altered adult neurogenesis appears precede appearance severe symptoms. Given scarcity human samples considerable differences with model species, increasingly complex stem-cell-based models being developed. These shedding light on alterations contribute development, facilitating new targets providing screening platform testing candidate drugs. Moreover, secretome other promising features cell types explored, use them replacement cells high plasticity or co-adjuvant therapy combinatorial treatments.

Language: Английский

Citations

0

Cell reprogramming: methods, mechanisms and applications DOI Creative Commons
Fei Zhu, Guangjun Nie

Cell Regeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 27, 2025

Abstract Cell reprogramming represents a powerful approach to achieve the conversion cells of one type into another interest, which has substantially changed landscape in field developmental biology, regenerative medicine, disease modeling, drug discovery and cancer immunotherapy. is complex ordered process that involves coordination transcriptional, epigenetic, translational metabolic changes. Over past two decades, range questions regarding facilitators/barriers, trajectories, mechanisms cell have been extensively investigated. This review summarizes recent advances mediated by transcription factors or chemical molecules, followed elaborating on important roles biophysical cues reprogramming. Additionally, this will detail our current understanding govern reprogramming, including involvement recently discovered biomolecular condensates. Finally, discusses broad applications future directions development, regenerative/rejuvenation therapy,

Language: Английский

Citations

0