Mohammed Hawash*, Mohammad Qneibi*, Hiba Natsheh, Noor Haj Mohammed, Lubaba Abu Hamda, Anil Kumar, Barbara Olech, Paulina Maria Dominiak, Sosana Bdir and Mohammad Bdair,
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引用次数: 0
Abstract
Parkinson’s disease (PD) is a significant health issue because it gradually damages the nervous system. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors play a significant role in the development of PD. The current investigation employed hybrid benzodioxole-propanamide (BDZ-P) compounds to get information on AMPA receptors, analyze their biochemical and biophysical properties, and assess their neuroprotective effects. Examining the biophysical characteristics of all the subunits of the AMPA receptor offers insights into the impact of BDZ-P on the desensitization and deactivation rate. It demonstrates a partial improvement in the locomotor capacities in a mouse model of Parkinson’s disease. In addition, the in vivo experiment assessed the locomotor activity by utilizing the open-field test. Our findings demonstrated that BDZ-P7 stands out with its remarkable potency, inhibiting the GluA2 subunit nearly 8-fold with an IC50 of 3.03 μM, GluA1/2 by 7.5-fold with an IC50 of 3.14 μM, GluA2/3 by nearly 7-fold with an IC50 of 3.19 μM, and GluA1 by 6.5-fold with an IC50 of 3.2 μM, significantly impacting the desensitization and deactivation rate of the AMPA receptor. BDZ-P7 showed an in vivo impact of partially reinstating locomotor abilities in a mouse model of PD. The results above suggest that the BDZ-P7 compounds show great promise as top contenders for the development of novel neuroprotective therapies.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research