Oligodendrocytes, the Forgotten Target of Gene Therapy DOI Creative Commons
Yasemin Güneş, Catherine Le Stunff, Pierre Bougnères

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1973 - 1973

Published: Nov. 28, 2024

If the billions of oligodendrocytes (OLs) populating central nervous system (CNS) patients could express their feelings, they would undoubtedly tell gene therapists about frustration with other neural cell populations, neurons, microglia, or astrocytes, which have been favorite targets transfer experiments. This review questions why OLs left out most therapy attempts. The first explanation is that pathogenic role still discussed in CNS diseases. Another reason so-called ubiquitous CAG, CBA, CBh, CMV promoters—widely used studies—are unable poorly able to activate transcription episomal transgene copies brought by adeno-associated virus (AAV) vectors OLs. Accordingly, expression has either not found evaluated studies rodents non-human primates. aims current are give rightful place among cells future target and encourage researchers test effect OL transduction various

Language: Английский

Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders DOI Creative Commons
Guangming Zhang,

Huayuan Wei,

Anliu Zhao

et al.

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 7, 2025

Mitochondrial dysfunction is a pivotal instigator of neuroinflammation, with mitochondrial DNA (mtDNA) leakage as critical intermediary. This review delineates the intricate pathways leading to mtDNA release, which include membrane permeabilization, vesicular trafficking, disruption homeostatic regulation, and abnormalities in dynamics. The escaped activates cytosolic sensors, especially cyclic gmp-amp synthase (cGAS) signalling inflammasome, initiating neuroinflammatory cascades via pathways, exacerbating spectrum neurological pathologies. therapeutic promise targeting discussed detail, underscoring necessity for multifaceted strategy that encompasses preservation homeostasis, prevention leakage, reestablishment dynamics, inhibition activation sensors. Advancing our understanding complex interplay between neuroinflammation imperative developing precision interventions disorders.

Language: Английский

Citations

3
Sympathetic and parasympathetic subtypes of body-first Lewy body disease observed in postmortem tissue from prediagnostic individuals DOI Creative Commons
Katrine B. Andersen, A. Krishnamurthy,

Mie Kristine Just

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Abstract Recent studies suggest the existence of brain-first and body-first subtypes within Lewy body disorder (LBD) spectrum, including Parkinson’s disease. These primarily focused on α-synuclein propagation through parasympathetic vagal olfactory bulb routes, leaving possibility a sympathetic nervous system spreading route unexplored. In present study, we analyzed two postmortem datasets, which included 173 129 cases positive for pathology. We observed clear distinction between in early prediagnostic with mild Brain-first displayed minimal peripheral organ pathology phases, contrasting marked autonomic involvement cases. Utilizing SuStaIn machine learning algorithm, identified distinct subtypes, one predominance another predominance, equal proportions. Our study supports three LBD highlights alongside onset progression.

Language: Английский

Citations

2
Therapeutic Role of Heterocyclic Compounds in Neurodegenerative Diseases: Insights from Alzheimer’s and Parkinson’s Diseases DOI Creative Commons
Nidhi Puranik, Minseok Song

Neurology International, Journal Year: 2025, Volume and Issue: 17(2), P. 26 - 26

Published: Feb. 7, 2025

Alzheimer’s and Parkinson’s are the most common neurodegenerative diseases (NDDs). The development of aberrant protein aggregates progressive permanent loss neurons major characteristic features these disorders. Although precise mechanisms causing disease (AD) (PD) still unknown, there is a wealth evidence suggesting that misfolded proteins, accumulation dysfunction neuroreceptors mitochondria, dysregulation enzymes, release neurotransmitters significantly influence pathophysiology diseases. There no effective protective medicine or therapy available even with availability numerous medications. an urgent need to create new powerful bioactive compounds since number people NDDs rising globally. Heterocyclic have consistently played pivotal role in drug discovery due their exceptional pharmaceutical properties. Many clinically approved drugs, such as galantamine hydrobromide, donepezil hydrochloride, memantine opicapone, feature heterocyclic cores. As therapeutic potential, heterocycles intriguing research topic for drugs PD AD. This review aims provide current insights into potential use targeting diverse targets manage potentially treat patients AD PD.

Language: Английский

Citations

1
Movement Disorders Society Viewpoint on Biological Frameworks of Parkinson's Disease: Current Status and Future Directions DOI Creative Commons
Lorraine V. Kalia, Daniela Berg,

Jeffery H. Kordower

et al.

Movement Disorders, Journal Year: 2024, Volume and Issue: 39(10), P. 1710 - 1715

Published: Sept. 9, 2024

Language: Английский

Citations

6
Recent advances in dynamic single-molecule analysis platforms for diagnostics: advantages over bulk assays and miniaturization approaches DOI
Dang Du Nguyen, Fedor A. Shuklin, Elena Barulina

et al.

Biosensors and Bioelectronics, Journal Year: 2025, Volume and Issue: 278, P. 117361 - 117361

Published: March 10, 2025

Language: Английский

Citations

0
The Gut–Brain Axis Based on α-Synuclein Propagation—Clinical, Neuropathological, and Experimental Evidence DOI Open Access
Ryōsuke Takahashi,

Hodaka Yamakado,

Norihito Uemura

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 3994 - 3994

Published: April 23, 2025

The cytopathological hallmark of Parkinson’s disease (PD) is a neuronal cytoplasmic inclusion called Lewy body (LB). bodies are composed alpha-synuclein (aSyn), 140 aa protein that predominantly expressed in the presynaptic terminal and which implicated neurotransmitter release. Recently, aSyn was found to propagate from neuron trans-synaptic manner. Although precise molecular mechanisms unclear, propagation believed play major role progression pathology PD. Neuropathologically, initial has been shown be formed dorsal motor nucleus vagus (DMV) or olfactory bulb by neuropathological studies. Since DMV innervates enteric nervous system (ENS) LBs gut nerve plexuses, it conceivable then other regions brain. In this article, clinical, neuropathological, experimental evidence supporting negating idea ENS brain leads PD reviewed. Moreover, seeds through systemic circulation multifocal generation discussed as potential alternative scenario for spreading

Language: Английский

Citations

0
The role of neuron-like cell lines and primary neuron cell models in unraveling the complexity of neurodegenerative diseases: a comprehensive review DOI
Kianoush Ghiasvand, Mehdi Amirfazli,

Parvaneh Moghimi

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Sept. 28, 2024

Language: Английский

Citations

2
Manganese Exposure Enhances the Release of Misfolded α-Synuclein via Exosomes by Impairing Endosomal Trafficking and Protein Degradation Mechanisms DOI Open Access
Dharmin Rokad, Dilshan S. Harischandra, Manikandan Samidurai

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12207 - 12207

Published: Nov. 14, 2024

Excessive exposure to manganese (Mn) increases the risk of chronic neurological diseases, including Parkinson's disease (PD) and other related Parkinsonisms. Aggregated α-synuclein (αSyn), a hallmark PD, can spread neighboring cells by exosomal release from neurons. We previously discovered that Mn enhances its spread, triggering neuroinflammatory neurodegenerative processes. To better understand Mn-induced αSyn, we examined effect on endosomal trafficking misfolded protein degradation. Exposing MN9D dopaminergic neuronal stably expressing human wild-type (WT) αSyn 300 μM for 24 h significantly suppressed mRNA expression Rab11a, thereby downregulating recycling, forcing late endosomes mature into multivesicular bodies (MVBs). Ectopic WT Rab11a mitigated exosome release, whereas ectopic mutant (S25N) increased it. Our in vitro vivo studies reveal upregulated (1) levels Rab27a, which mediates fusion MVBs with plasma membrane; (2) autophagosomal markers Beclin-1 p62, but downregulated lysosomal marker LAMP2, impairing autophagolysosome formation as confirmed LysoTracker, cathepsin, acridine orange assays. novel findings demonstrate promotes

Language: Английский

Citations

2
Oligodendrocytes, the Forgotten Target of Gene Therapy DOI Creative Commons
Yasemin Güneş, Catherine Le Stunff, Pierre Bougnères

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1973 - 1973

Published: Nov. 28, 2024

If the billions of oligodendrocytes (OLs) populating central nervous system (CNS) patients could express their feelings, they would undoubtedly tell gene therapists about frustration with other neural cell populations, neurons, microglia, or astrocytes, which have been favorite targets transfer experiments. This review questions why OLs left out most therapy attempts. The first explanation is that pathogenic role still discussed in CNS diseases. Another reason so-called ubiquitous CAG, CBA, CBh, CMV promoters—widely used studies—are unable poorly able to activate transcription episomal transgene copies brought by adeno-associated virus (AAV) vectors OLs. Accordingly, expression has either not found evaluated studies rodents non-human primates. aims current are give rightful place among cells future target and encourage researchers test effect OL transduction various

Language: Английский

Citations

0