Targeting the pathogenesis and boosting the therapeutic efficacy of Parkinson's disease by advanced nanoparticles DOI Creative Commons
Hanghang Liu,

Menglong Hua,

Qing Yin Zheng

et al.

MedComm – Biomaterials and Applications, Journal Year: 2023, Volume and Issue: 2(2)

Published: June 1, 2023

Abstract With the aging of global population, early diagnosis and treatment neurodegenerative diseases such as Parkinson's disease (PD) have attracted considerable attention. Despite great advances achieved during past decades, PD second largest is still incurable. In clinical practice, patients are mainly treated by drugs, supplemented with deep brain stimulation or nerve nucleus destruction. The existing drugs can only relieve symptoms motor disorder, cannot stop progression PD. Compared small molecular nanoparticles exhibit multiple functions in neuroprotection neurorepair due to their tunable physical chemical properties, easy modification functionalization. Herein, we first briefly review characteristics crossing blood–brain barrier, which a primary challenge for Then, summarize pathologic mechanisms comprehensively discuss novel therapy based on diverse nanoparticles, including alleviating oxidative stress, scavenging α‐synuclein aggregates, chelating metal ions, delivering neurotrophic factors genes, transplanting stem cells. This aims highlight potential advanced

Language: Английский

3′-epi-12β-hydroxyfroside-mediated autophagy degradation of RIPK1/RIPK3 necrosomes leads to anergy of immunogenic cell death in triple-negative breast cancer cells DOI Creative Commons
Feng‐Ying Huang,

Shu-Zhen Dai,

Wentian Xu

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106613 - 106613

Published: Dec. 16, 2022

Increasing studies have suggested that some cardiac glycosides, such as conventional digoxin (DIG) and digitoxin, can induce immunogenic cell death (ICD) in various tumors. We previously found 3'-epi-12β-hydroxyfroside (HyFS), a novel cardenolide compound isolated by our group, could cytoprotective autophagy through inactivation of the Akt/mTOR pathway. However, whether HyFS ICD remains unknown. In this study, we extend work to further investigate both ICD, investigated relationship between three TNBC lines. Unexpectedly, compared DIG, complete flux but not human triple-negative breast cancer (TNBC) lines one murine model. Inhibition HyFS-induced resulted production MDA-MB-231, MDA-MB-436, HCC38 cells. A mechanism study showed formation RIPK1/RIPK3 necrosomes was necessary for induction DIG-treated cells, while treatment led receptor-interacting serine-threonine kinase (RIPK)1/3 necrosome degradation via an process. Additionally, inhibition inhibitor chloroquine reoccurrence reversion tumor microenvironment, leading more significant antitumor effects immunocompetent mice than immunodeficient mice. These findings indicate HyFS-mediated autophagic leads Moreover, combined with may enhance activities, suggesting alternative therapeutic treatment.

Language: Английский

Citations

22
GBA1-Associated Parkinson’s Disease Is a Distinct Entity DOI Open Access
Aliaksandr Skrahin, Mia Horowitz, Majdolen Istaiti

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7102 - 7102

Published: June 28, 2024

-associated Parkinson's disease (

Language: Английский

Citations

4
PLK2 disrupts autophagic flux to promote SNCA/α-synuclein pathology DOI Creative Commons
Chuang Zhang, Zhan-Peng Huang, Xinyue Huang

et al.

Autophagy, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 21

Published: Jan. 8, 2025

The aggregation and transmission of SNCA/α-synuclein (synuclein, alpha) is a hallmark pathology Parkinson disease (PD). PLK2 (polo like kinase 2) an evolutionarily conserved serine/threonine that more abundant in the brains all family members, highly expressed PD, linked to SNCA deposition. However, addition its role phosphorylating SNCA, PD mechanisms involved triggering neurodegeneration remain unclear. Here, we found regulated independently S129. Overexpression promoted preformed fibril (PFF)-induced wild-type mutant SNCAS129A. Genetic or pharmacological inhibition attenuated deposition neurotoxicity. Mechanistically, exacerbated propagation by impeding clearance aggregates blocking macroautophagic/autophagic flux. We further showed phosphorylated S1098 DCTN1 (dynactin 1), protein controls movement organelles, leading impaired autophagosome-lysosome fusion. Furthermore, genetic suppression alleviated motor dysfunction vivo. Our findings suggest negatively regulates autophagy, promoting pathology, suggesting for PD.

Language: Английский

Citations

0
Apigenin enhances Nrf2-induced chaperone-mediated autophagy and mitigates α-synuclein pathology: Implications for Parkinson's disease therapy DOI
Yibin Huang, Lulu Tian,

Ziwen Zhu

et al.

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156652 - 156652

Published: March 1, 2025

Language: Английский

Citations

0
TM9SF1 inhibits colorectal cancer metastasis by targeting Vimentin for Tollip-mediated selective autophagic degradation DOI Creative Commons
Huifen Wang, Jia Hu, Di Wang

et al.

Cell Death and Differentiation, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

Citations

0
Acid-Resistant and Viscosity-Sensitive Proteome Aggregation Sensor To Visualize Cellular Aggrephagy in Live Cells and Clinical Samples DOI

Jintai Deng,

Wang Wan, Rui Sun

et al.

ACS Sensors, Journal Year: 2025, Volume and Issue: unknown

Published: April 6, 2025

Aggrephagy in cells is defined as the degradation of intracellular aggregated proteins via macroautophagy process. This process sequesters protein aggregates into autolysosomes, which bear characteristic viscous and acidic microenvironments. Limited aggregation sensors are environmentally compatible with cellular aggrephagy Here, we report an acid-resistant viscosity-sensitive proteome sensor to detect stressed clinical samples. fluoresces upon selectively ubiquitously binding different proteins. Importantly, unlike other reported sensors, our probe offers unique fluorescence inside proteins, enabling its application autolysosome microenvironment. In live under various conditions, optimal (A6) successfully detects validated by colocalization a lysosomal tracker. Additionally, demonstrate that can heat-stressed tissue samples biopsied from cancer patients undergoing thermal perfusion treatment. Together, facilitates detection chemically matching microenvironmental characteristics.

Language: Английский

Citations

0
Pterostilbene alleviates MPTP-induced neurotoxicity by targeting neuroinflammation and oxidative stress DOI

Yepeng Fan,

Feng He, Mulan Chen

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 729, P. 150358 - 150358

Published: July 5, 2024

Language: Английский

Citations

3
Non-invasive auditory and visual stimulation attenuates α-Synuclein deposition and improves motor and non-motor symptoms in PD mice DOI
Yuntao Liu, Haiwei Liu,

Yingwen Lu

et al.

Experimental Neurology, Journal Year: 2023, Volume and Issue: 364, P. 114396 - 114396

Published: March 31, 2023

Language: Английский

Citations

8
Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the Caenorhabditis elegans Model DOI Creative Commons
Ru‐Huei Fu, Syuan‐Yu Hong, Hui‐Jye Chen

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(18), P. 2310 - 2310

Published: Sept. 19, 2023

Defective autophagy is one of the cellular hallmarks Parkinson's disease (PD). Therefore, a therapeutic strategy could be modest enhancement autophagic activity in dopamine (DA) neurons to deal with clearance damaged mitochondria and abnormal protein aggregates. Syringin (SRG) phenolic glycoside derived from root Acanthopanax senticosus. It has antioxidant, anti-apoptotic, anti-inflammatory properties. However, whether it preventive effect on PD remains unclear. The present study found that SRG reversed increase intracellular ROS-caused apoptosis SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, C. elegans, degeneration DA neurons, DA-related food-sensitive behaviors, longevity, accumulation α-synuclein were also improved. Studies neuroprotective mechanisms have shown can reverse suppressed expression SIRT1, Beclin-1, other markers 6-OHDA-exposed cells. Thus, these enhanced formation vacuoles activity. This protective blocked pretreatment wortmannin (an autophagosome blocker) bafilomycin A1 autophagosome-lysosome fusion blocker). In addition, increases acetylation leading its inactivation. induce SIRT1 promote deacetylation Beclin-1. Finally, we reduced 6-OHDA-induced miR-34a targeting SIRT1. overexpression mimic abolishes ability SRG. conclusion, induces via partially regulating miR-34a/SIRT1/Beclin-1 axis prevent accumulation. opportunity established as candidate agent for prevention cure PD.

Language: Английский

Citations

7
A systematic exploration of unexploited genes for oxidative stress in Parkinson’s disease DOI Creative Commons
Takayuki Suzuki, Hidemasa Bono

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

Published: Aug. 17, 2024

Human disease-associated gene data are accessible through databases, including the Open Targets Platform, DisGeNET, miRTex, RNADisease, and PubChem. However, missing entries in such databases anticipated because of curational errors, biases, text-mining failures. Additionally, extensive research on human diseases has led to challenges registering comprehensive data. The lack essential hinders knowledge sharing should be addressed. Therefore, we propose an analysis pipeline explore unexploited genes databases. Using this for Parkinson's disease with oxidative stress revealed two genes: nuclear protein 1 (NUPR1) ubiquitin-like PHD ring finger domains 2 (UHRF2). This methodology enhances identification underrepresented genes, facilitating easier access potential disease-related functional genes. study aims identify further does not include independent experimental validation.

Language: Английский

Citations

2