AaTs-1, a Tetrapeptide from Scorpion Venom Mitigates Demyelination and Neuroinflammation in a Cuprizone-Induced Model of Multiple Sclerosis

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  AaTs-1, a Tetrapeptide from Scorpion Venom Mitigates Demyelination and Neuroinflammation in a Cuprizone-Induced Model of Multiple Sclerosis Abstract Purpose This study focuses on the evaluation of the therapeutic potential of Tetrascorpin-1 (AaTs-1), a tetrapeptide isolated from Androctonus australis hector venom, proposed as a putative formyl peptide receptor 2 (FPR2) antagonist, in a cuprizone-induced murine model of Multiple sclerosis (MS), a chronic autoimmune and inflammatory disease of the central nervous system. Methods Acute demyelination was induced in mice by administering cuprizone (0.2% w/w in the diet) for six weeks. During the sixth week of cuprizone intake, demyelinated mice received intranasal administration of AaTs-1 at a dose of 50–100 µg/kg for five consecutive days, with 24-hour intervals between treatments. Results Behavioral assessments, immunological assays, and histological analyses revealed that AaTs-1 improved body weight, reduced behavioral impairments...

Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. variegata

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Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. variegata

Abstract

Brown spider envenomation (loxoscelism) represents a significant public health concern in South America, yet most studies focus on a few medically recognized species. Here, we provide the first molecular and functional characterization of the venom gland extract from Loxosceles aff. variegata (LafvVGE), a brown spider collected in synanthropic habitats in Ituiutaba, Minas Gerais, Brazil. SDS-PAGE and immunoblot analyses revealed prominent protein bands consistent with phospholipase D (PLD) toxins, the main agents of loxoscelism symptoms. ELISA assays demonstrated that LafvVGE is effectively recognized by Brazilian therapeutic antivenoms, indicating immunological cross-reactivity. Enzymatic assays confirmed sphingomyelinase and collagenase/gelatinase activities comparable to those of Loxosceles gaucho (a species of acknowledged medical relevance), although LafvVGE from female individuals showed higher activities than male derived pools under our experimental conditions. Neutralization assays showed complete inhibition of sphingomyelinase activity but only partial inhibition of gelatinase activity by the anti-loxoscelic antivenom, highlighting differential susceptibility of venom components to antivenom-mediated neutralization under in vitro conditions. Molecular analysis of venom gland transcripts identified eight distinct PLD isoforms (LafvPLD1–8), all containing conserved catalytic and metal-binding residues characteristic of class II Loxosceles PLDs. Structural modeling revealed isoform-specific variations in the aromatic cage motif and electrostatic surface, suggesting potential effects on membrane interactions and substrate specificity. Collectively, these findings place L. aff. variegata within the biochemical and structural spectrum of medically relevant Loxosceles species, expanding comparative knowledge of PLD diversity and function. While clinical relevance remains to be established in vivo, this study underscores the value of integrating biochemical, immunological, and structural analyses to identify emerging venom phenotypes with potential implications for surveillance and antivenom coverage.
Silva-Araújo, A. L., Silva-Magalhães, R., Peres-Damásio, P., Pereira, E. H. T., De Oliveira Souza, R., Varela, L. S. D. R. N., Ribeiro Tomé, L. M., Campos de Melo Iani, F., Silveira, A. L., Borges, M. H., Medina-Santos, R., Chavez-Olórtegui, C., Vasconcelos Diniz, M. R., Bittencourt Paiva, A. L., & Guerra-Duarte, C. (2026). Venom characterization and structural insights into phospholipase D isoforms from the spider Loxosceles aff. Variegata. Toxicon, 109129. https://doi.org/10.1016/j.toxicon.2026.109129