β-asarone, an effective volatile oil component of Acorus chinensis, has been found to hold beneficial effects on Parkinson's disease (PD), but its mechanism remains incompletely understood. Drosophila melanogaster with PTEN induced kinase 1 (PINK1) mutations, a prototype PD model, was used in this study. We found that calcium chelation profoundly alleviated a spectrum of PD symptoms. Whereas, calcium supplementation made the case worse, suggesting accumulated calcium contributes to progression of PD. β-asarone administration decreased Ca level in PD flies, accompanied by alleviated behavioral and neural defects. Further study demonstrated that β-asarone downregulated L-type Ca channels (Dmca1D), which was increased in PD flies. Besides, β-asarone decreased expression of 1,4,5 - trisphosphate receptor (Itpr), which is responsible for calcium release from endoplasmic reticulum (ER). Knockdown of either Dmca1D or Itpr specifically in dopaminergic neurons alleviated behavioral and neural defects in PD flies. While overexpression of Itpr aggravated PD symptoms. The results indicated that increased intracellular calcium influx and release triggers dysregulation of calcium homeostasis in PD flies. And β-asarone prevents PD by restoring Ca homeostasis. Overall, the study demonstrated that β-asarone can serve as a new prospective medication against PD or other diseases associated with dysregulation of Ca homeostasis.
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http://dx.doi.org/10.1016/j.ejphar.2024.177155 | DOI Listing |
Med Chem
January 2025
Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco.
Background: Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential.
View Article and Find Full Text PDFCNS Neurol Disord Drug Targets
January 2025
Department of Biotechnology, National Institute of Technology, Raipur, 492001, India.
Parkinson's disease (PD) is a neurodegenerative disorder that results from the progressive loss of neurons in the brain followed by symptoms such as slowness and rigidity in movement, sleep disorders, dementia and many more. The different mechanisms due to which the neuronal degeneration occurs have been discussed, such as mutation in PD related genes, formation of Lewy bodies, oxidation of dopamine. This review discusses current surgical treatment and gene therapies with novel developments proposed for PD.
View Article and Find Full Text PDFCNS Neurol Disord Drug Targets
January 2025
Department of Pharmaceutical Chemistry, Delhi Pharmaceutical Sciences & Research University, Delhi, India-110017.
Neurodisease, caused by undesired substances, can lead to mental health conditions like depression, anxiety and neurocognitive problems like dementia. These substances can be referred to as contaminants that can cause damage, corruption, and infection or reduce brain functionality. Contaminants, whether conceptual or physical, have the ability to disrupt many processes.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2025
Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 Str, 02-106 Warsaw, Poland.
The purpose of this review was to analyse the literature regarding the correlation between the level of tryptamine, aryl hydrocarbon receptor (AHR) signalling pathway activation, and monoamine oxidase (MAO)-A and MAO-B activity in health and conditions such as neurodegenerative, neurodevelopmental, and psychiatric disorders. Tryptamine is generated through the decarboxylation of tryptophan by aromatic amino acid decarboxylase (AADC) in the central nervous system (CNS), peripheral nervous system (PNS), endocrine system, and gut bacteria. Organ-specific metabolism of tryptamine, which is mediated by different MAO isoforms, causes this trace amine to have different pharmacokinetics between the brain and periphery.
View Article and Find Full Text PDFEndocr Metab Immune Disord Drug Targets
January 2025
Department of Laboratory Medicine, Taizhou First People's Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, Zhejiang, China.
Aim: The aim of this study is to examine the role of the microrchidia (MORC) family, a group of chromatin remodeling proteins, as the therapeutic and prognostic markers for colorectal cancer (CRC).
Background: MORC protein family genes are a highly conserved nucleoprotein superfamily whose members share a common domain but have distinct biological functions. Previous studies have analyzed the roles of MORCs as epigenetic regulators and chromatin remodulators; however, the involvement of MORCs in the development and pathogenesis of CRC was less examined.
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