The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway

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  The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway Abstract Introduction:  Voltage-gated sodium channel (VGSC) dysregulation, particularly of the Nav1.6 subtype, is a core mechanism underlying epileptogenesis and its associated neuropsychiatric comorbidities. The scorpion venom peptide BmK AS has demonstrated anticonvulsant potential, but its efficacy in chronic epilepsy and the precise mechanisms of action remain undefined. Methods:  Here, we show that BmK AS exerts robust anti-epileptic and neuroprotective effects through converging mechanisms. In a kainic acid-induced mouse model, BmK AS treatment reduced mortality and seizure parameters. Electrophysiological studies assessed BmK AS modulation of VGSC subtypes. The functional relevance of Nav1.6 targeting was confirmed by the loss of BmK AS’s anti-seizure efficacy upon its pharmacological blockade in a PTZ-in...

Exploring Venom-derived Peptides from Calloselasma rhodostoma Snake as Promising Cholinesterase Inhibitors for Alzheimer’s Disease Therapy

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By Wibowo Djatmiko (Wie146) - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=21623901

Exploring Venom-derived Peptides from Calloselasma rhodostoma Snake as Promising Cholinesterase Inhibitors for Alzheimer’s Disease Therapy

Alzheimer’s disease (AD) is a neurodegenerative disorder that primarily affects individuals over 60 years of age, characterized by symptoms such as memory impairment and cognitive decline. The pathogenesis of AD involves multiple factors, including protein misfolding and oxidative stress. A crucial aspect of AD progression is the dysregulation of cholinesterase enzymes, particularly acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which contribute to neurotoxic amyloid plaques and neurofibrillary tangles. This study investigates the potential of proteins and peptides from the venom of Calloselasma rhodostoma as BChE inhibitors, aiming to explore new therapeutic avenues for AD. Venom was extracted, fractionated, and analyzed using ultrafiltration, SDS-PAGE, and LC-HRMS. In vitro assays evaluated the BChE inhibition activity, while in silico molecular docking assessed the binding affinities of the identified peptides. The study identified several venom-derived peptides with significant BChE inhibitory potential, notably CFVVQPWEGK and IDVLSDEPR, which demonstrated strong binding affinities and stability in docking studies. These findings highlight the potential of peptides derived from C. rhodostoma venom as natural BChE inhibitors, offering a promising basis for developing novel AD therapies. Further research is warranted to fully understand the mechanisms and therapeutic potential of these bioactive compounds.

Exploring Venom-derived Peptides from Calloselasma rhodostoma Snake as Promising Cholinesterase Inhibitors for Alzheimer’s Disease Therapy

Annisa Maghfira, Itsar Auliya, Tri Rini Nuringtyas, Fajar Sofyantoro, Donan Satria Yudha, Slamet Raharjo, and Yekti Asih Purwestri