An AIE-based fluorescent probe to detect peroxynitrite levels in human serum and its cellular imaging DOI
Jaewon Kim,

Jiyoung Yoo,

Byungkook Kim

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(41), P. 5443 - 5446

Published: Jan. 1, 2024

Presenting Mt-NI-2: a fluorescent probe for peroxynitrite levels in human serum and mitochondria. It utilizes as diagnostic tool neurodegenerative diseases, facilitating in-depth exploration of their underlying mechanisms.

Language: Английский

Targeting mitophagy in neurodegenerative diseases DOI
Odetta Antico, Paul Thompson, Nicholas T. Hertz

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

Citations

6
Neuroimaging and fluid biomarkers in Parkinson’s disease in an era of targeted interventions DOI Creative Commons
Angeliki Zarkali, George E. Thomas, Henrik Zetterberg

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 5, 2024

Abstract A major challenge in Parkinson’s disease is the variability symptoms and rates of progression, underpinned by heterogeneity pathological processes. Biomarkers are urgently needed for accurate diagnosis, patient stratification, monitoring progression precise treatment. These were previously lacking, but recently, novel imaging fluid biomarkers have been developed. Here, we consider new approaches showing sensitivity to brain tissue composition, examine specificity processes, including seed amplification assays extracellular vesicles. We reflect on these context biological staging systems, emerging techniques currently development.

Language: Английский

Citations

14
Parkinson’s Disease Drug Therapies in the Clinical Trial Pipeline: 2024 Update DOI Creative Commons

Kevin McFarthing,

Sue Buff,

Gary Rafaloff

et al.

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(5), P. 899 - 912

Published: July 19, 2024

For the past five years, our annual reports have been tracking clinical development of new drug-based therapies for neurodegenerative condition Parkinson's disease (PD). These reviews followed progress both "symptomatic treatments" (ST - improves/reduces symptoms condition) and "disease-modifying (DMT attempts to delay/slow progression by addressing underlying biology PD). Efforts also made further categorize these experimental treatments based on their mechanisms action class drug.

Language: Английский

Citations

13
A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells DOI Creative Commons
Yahaira Naaldijk, Belén Fernández, Rachel Fasiczka

et al.

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

Published: Jan. 8, 2024

Abstract Parkinson´s disease (PD) is a common neurodegenerative movement disorder and leucine-rich repeat kinase 2 (LRRK2) promising therapeutic target for intervention. However, the ability to stratify patients who will benefit from such treatment modalities based on shared etiology critical success of disease-modifying therapies. Ciliary centrosomal alterations are commonly associated with pathogenic LRRK2 activity can be detected in many cell types. We previously found deficits immortalized lymphocytes G2019S-LRRK2 PD patients. Here, investigate whether may serve as potential blood biomarker which susceptible LRKK2 inhibitor treatment, we characterized patient-derived cells distinct cohorts. report peripheral subset early-stage idiopathic mitigated by inhibition, supporting role aberrant PD. Centrosomal defects R1441G-LRRK2 non-manifesting mutation carriers, indicating that they accumulate prior clinical diagnosis. They present well primary blood. These findings indicate analysis blood-based patient stratification help nominate LRRK2-related therapeutics.

Language: Английский

Citations

11
G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage DOI Creative Commons
Nicholas Pena,

Tara Richbourg,

Claudia P. González-Hunt

et al.

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

Published: March 1, 2024

Abstract Pathogenic mutations in LRRK2 cause Parkinson’s disease (PD). The G2019S variant is the most common, which results abnormally high kinase activity. Compounds that target activity are currently being developed and tested clinical trials. We recently found causes mitochondrial DNA (mtDNA) damage treatment with multiple classes of inhibitors at concentrations associated dephosphorylation reversed mtDNA to healthy control levels. Because maintaining normal function heterozygous carriers while specifically targeting could have an advantageous safety profile, we explored efficacy a mutant selective inhibitor reverse models patient cells relative non-selective inhibitors. Potency inhibition by EB-42168, inhibitor, MLi-2, was determined measuring phosphorylation Ser935 and/or Ser1292 using quantitative western immunoblot analysis. Mito DX assay, allows for accurate real-time quantification 96-well platform, performed parallel. confirmed EB-42168 selectively inhibits on wild-type LRRK2. On other hand, MLi-2 equipotent Acute inhibited also restored further investigated relationship between activity, mitophagy. Levels caused were fully re-established within 2 h wash out recovery experiment, indicating phenotype highly dynamic. mitophagy defects not alleviated inhibition, suggesting mechanistically regulating kinase-mediated reversal this acute timeframe. Abrogation tool demonstrates potential precision medicine approach PD. may serve as pharmacodynamic biomarker altered be useful small molecule development

Language: Английский

Citations

9
LONG-RANGE PCR AS A TOOL FOR EVALUATING MITOCHONDRIAL DNA DAMAGE: PRINCIPLES, BENEFITS, AND LIMITATIONS OF THE TECHNIQUE DOI
Artem P. Gureev, Veronika V. Nesterova, Irina S. Sadovnikova

et al.

DNA repair, Journal Year: 2025, Volume and Issue: 146, P. 103812 - 103812

Published: Jan. 18, 2025

Language: Английский

Citations

1
Mitochondrial DNA (mtDNA) as fluid biomarker in neurodegenerative disorders: A systematic review DOI Creative Commons
Barbara Risi, Alberto Imarisio,

Giada Cuconato

et al.

European Journal of Neurology, Journal Year: 2025, Volume and Issue: 32(1)

Published: Jan. 1, 2025

Abstract Background Several studies evaluated peripheral and cerebrospinal fluid (CSF) mtDNA as a putative biomarker in neurodegenerative diseases, often yielding inconsistent findings. We systematically reviewed the current evidence assessing blood CSF levels variant burden Parkinson's disease (PD), Alzheimer's (AD) amyotrophic lateral sclerosis (ALS). Multiple (MS) was also included paradigm of chronic neuroinflammation‐driven neurodegeneration. Methods Medline, Embase, Scopus Web Science were searched for articles published from inception until October 2023. Studies focused on haplogroups or hereditary pathogenic variants excluded. Critical appraisal performed using Quality Assessment Diagnostic Accuracy criteria. Results Fifty‐nine original met our priori‐defined inclusion The majority CSF‐focused showed (i) decreased PD AD; (ii) increased MS compared to controls. No ALS. cell‐free intracellular contradictory, even within evaluating same disease. This poor reproducibility is likely due lack consideration many factors known affect levels. damage methylation reduced patients controls, respectively. A few investigated correlation between severity, with conflicting results. Conclusions Additional well‐designed are needed evaluate profiles biomarkers diseases. identification “mitochondrial subtypes” may enable novel precision medicine strategies counteract

Language: Английский

Citations

1
LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting DOI
Yulan Xiong, Jianzhong Yu

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(10), P. 982 - 996

Published: Aug. 16, 2024

Language: Английский

Citations

7
Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases DOI
Zeming Wu, Jing Qu, Guang‐Hui Liu

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(12), P. 979 - 1000

Published: Oct. 3, 2024

Language: Английский

Citations

7
Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma DOI
Xinying Liu, Jiaxin Zhang,

Shunzhe Zheng

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 370, P. 168 - 181

Published: April 24, 2024

Language: Английский

Citations

6