Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 149 - 149

Published: Jan. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Language: Английский

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Protective effects of harpagoside on mitochondrial functions in rotenone‑induced cell models of Parkinson's disease

Biomedical Reports, Journal Year: 2025, Volume and Issue: 22(4)

Published: Feb. 11, 2025

Parkinson's disease (PD) is the second most common neurodegenerative after Alzheimer's disease. Currently, no radical treatment available for this Harpagoside a proposed neuroprotective iridoid active ingredient that can be derived from Scrophulariae buergeriana, Scrophularia striata and Harpagophytum procumbens. The present study aimed to investigate effects of harpagoside on mitochondrial functions in rotenone-induced cell models (PD). Neuro-2A (N2A) cells were treated with rotenone establish vitro PD. Cell viability survival measured using Counting Kit-8 assay. Biochemical assays spectrophotometry used measure complex I activity, swelling caspase 3 activity. rate was first found significantly decreased by (20 nmol/l) treatment. However, intervention (10 µmol/l) increase N2A differentiated 1 mmol/l dibutyryl-cAMP. At ≥0.1 µmol/l concentration, alleviated swelling, whereas at it counteracted inhibitory 10 inhibited activation. These results suggest has potential protect against injury

Language: Английский

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Next Generation Sequencing Analysis in Patients Affected by Parkinson’s Disease and Correlation Between Genotype and Phenotype in Selected Clinical Cases

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2397 - 2397

Published: March 7, 2025

Parkinson’s Disease (PD) is the most frequent movement disorder and second only to Alzheimer’s as neurodegenerative pathology. Early onset disease (EOPD) less common may be characterized by genetic predisposition. NGS testing might useful in diagnostic assessment of these patients. A panel eight genes (SNCA, PRKN, PINK1, DJ1, LRRK2, FBXO7, GBA1 HFE) was validated used a tool. total 38 sequence EOPD patients Unit our Hospital Institution were tested. In addition, number hexanucleotide repeats C9ORF72 gene frequency main HFE mutations evaluated. Six carriers likely pathogenic heterozygosity analyzed genes, one them presented association another had complex background. Their clinical symptoms correlated with their genotypes. cohort patients, p.Cys282Tyr significantly decreased dominant model allele contrast comparison. Only patient containing 10 identified clinically described. The signs sporadic monogenic PD are often very similar; for this reason, it fundamental correlate genotypes phenotypes, we tried describe here, better classify aim deepen knowledge molecular mechanisms involved collaborate reaching personalized management treatment.

Language: Английский

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Multicomponent Mendelian randomization and machine learning studies of potential drug targets for neurodegenerative diseases

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Neurodegenerative diseases (NDDs) remain a global health challenge. Alzheimer's disease (AD) and Parkinson's (PD) are the main types of NDDs worldwide, Mendelian Randomization (MR) analysis across multi-omics entire genome offers novel strategies for identifying potential drug targets. This study used MR summary-based MR(SMR) to explore causal relationship between genes NDDs. Colocalization machine learning further validated reinforced findings. The pharmacological activity candidate targets was confirmed via molecular docking Molecular dynamics. revealed 14 that were closely associated with both Specifically, IQCE(AD), HDHD2(AD), COMMD10(AD), ALPP (AD), FXYD6 STK3 (PD), LHFPL2 ENPP4 identified as risk factors (OR > 1), whereas HEXIM2 TSC22D4 CHRNB1 BAG4 SLC25A1 IL15 protective < 1). results strong binding activities PREDNISOLONE(ALPP = -7.6 kcal/mol), PANCURONIUM BROMIDE(CHRNB1 -8 CHEMBL379975(STK3 =-10.7 kcal/mol) SIROLIMUS(IL15 -9 kcal/mol). dynamics simulations stable IL15-Sirolimus, ALPP-Prednisolone, STK3-CHEMBL379975, CHRNB1-Rocuronium bromide complexes. promising therapeutic NDDs, providing new insights targeted therapies clinical Our provide evidence future studies aimed at developing appropriate interventions.

Language: Английский

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