DefinePK

Abstract

Our research explores the interaction between 2-(4-Butoxyphenyl)-N-hydroxyacetamide and CISD1, highlighting its potential benefits in treating age-related Parkinson’s disease (PD). PD is a neurodegenerative disorder characterised by the gradual deterioration of the nervous system, leading to cognitive dysfunction, memory lapses, and motor disabilities. CISD1, a member of the CDGSH iron-sulfur domain protein family, is crucial for mitochondrial and endoplasmic reticulum (ER) integrity and calcium regulation. Systems biology analyses reveal that CISD1 plays a key role in essential cellular processes, and its decline with age contributes to premature ageing symptoms. Loss of CISD1 function is linked to ageing-related phenotypes such as mitochondrial dysfunction, impaired autophagy, increased oxidative stress, and cell death. Specifically, CISD1 loss disrupts the electron transport chain, leading to ER stress, increased reactive oxygen species (ROS) generation, and impaired intracellular calcium homeostasis, ultimately reducing mitochondrial oxidative phosphorylation efficiency. Computer-aided drug design analyses indicate that CISD1 dysfunction affects key tissues, including the brain, spinal cord, heart, skeletal muscle, and skin. Computational predictions suggest that 2-(4-Butoxyphenyl)-N-hydroxyacetamide may serve as a potential CISD1 activator. Overall, this study suggests that 2-(4-Butoxyphenyl)-N-hydroxyacetamide could counteract telomere shortening and play a therapeutic role in age-related Parkinson’s disease by restoring mitochondrial function and cellular homeostasis.