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Last update 08 May 2025

LMLN

Last update 08 May 2025

Basic Info

Synonyms

Gp63, Invadolysin, leishmanolysin like peptidase

+ [4]

Introduction

Metalloprotease.

Drugs associated with LMLN

Leishmania multi-epitope vaccine(Shiraz University of Medical Sciences)

Target

GNB1L x LMLN

Mechanism

GNB1L modulators [+1]

Active Org.

Shiraz University of Medical Sciences

Originator Org.

Shiraz University of Medical Sciences

Active Indication

Leishmaniasis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with LMLN

100 Translational Medicine associated with LMLN

0 Patents (Medical) associated with LMLN

505

Literatures (Medical) associated with LMLN

01 Jun 2025·Microbial Pathogenesis

Dual RNA-Seq reveals strain-specific transcriptional adaptations of Trypanosoma cruzi in host cells infected with isolates from acute and chronic cases

Article

Author: Cruz-Saavedra, Lissa ; Ramírez, Juan David ; Velandia, Sofia ; Cantillo-Barraza, Omar ; Patiño, Luz Helena

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health issue, particularly in Latin America, and is traditionally transmitted by triatomine bugs. Chagas disease progresses through two phases: an acute phase characterized by high parasitemia and a chronic phase, which may remain asymptomatic or develop into severe complications. This study utilized dual-RNAseq technology to analyze gene expression in mice fibroblast host cells infected with the strain JJ21 isolated from an acute Chagas disease case of presumptive oral transmission, comparing it with the MG strain isolated from a chronic Chagas disease human case. The results revealed that JJ21 exhibits a distinct transcriptional profile, marked by the up-regulation of immune evasion and stress response genes, suggesting specific adjustments to meet the demands of the acute phase. At 24 h post-infection, host cells exhibited increased expression of genes related to immune recognition, cargo receptor activity, and pro-inflammatory responses, indicating a robust initial defensive reaction. By 72 h, the host response shifted towards stress management and antioxidant activity, reflecting efforts to handle prolonged infection. Comparative analysis with the MG strain revealed significant differences: JJ21 showed notable up-regulation of mucin and down-regulation of dynein, indicating unique strategies for evading immune responses and altering intracellular interactions. The heightened expression of virulence factors such as trans-sialidases (Ts) and GP63 proteins in JJ21 supports this hypothesis. In conclusion, this study reveals how the JJ21 strain's unique pro-inflammatory response and adaptive strategies enhance our understanding of strain specific responses during the Chagas disease. These insights are crucial for developing targeted interventions and vaccines to more effectively manage the disease and its global impact.

01 May 2025·Journal of Biological Chemistry

Evolutionary duplication of the leishmanial adaptor protein α-SNAP plays a role in its pathogenicity

Article

Author: Dey, Chinmoy Sankar ; Datta, Shankari Prasad

Essential-gene duplication during evolution promotes specialized functions beyond the typical role. Our in silico study unveiled two α-SNAP paralogs in Leishmania, a crucial component that, along with NSF, triggers disassembly of the cis-SNARE complex, formed during vesicle fusion with target membranes. While multiple α-SNAPs are common in many flagellated protists, including the trypanosomatids, they are unusual among other eukaryotes. This study explores the evolutionary and functional relevance of α-SNAP gene duplication in Leishmania donovani, emphasizing both subfunctionalization and neofunctionalization. We discovered that L. donovani α-SNAP (Ldα-SNAP) genes are transcribed in promastigote and amastigote stages, indicating they are not pseudogenes. Although the two paralogs share essential residues and structural features, only Ldα-SNAP₁₆₆₀ (Ldα-SNAP1) can effectively substitute the function of its yeast counterpart, while Ldα-SNAP₃₀₄₀ (Ldα-SNAP2) cannot. This functional difference is attributed to a replacement of alanine with phosphorylatable-serine in Ldα-SNAP1 during evolution from the most common ancestral ortholog. This modification is rarely observed in corresponding orthologs of other trypanosomatids. Incidentally, Ldα-SNAP paralogs exhibit differential localization in the ER and flagellar pocket. However, both paralogs, either actively or passively, regulate the secretion of exosomes and PM blebs, containing the virulence protein GP63. This indicates functional division and their indirect participation in the host's macrophage inactivation. Moreover, a small fraction of Ldα-SNAP1's presence in the flagellum hints at a potential role in sensing environmental cues and aiding the parasite's attachment to the sandfly's hindgut. Our findings underscore that duplicated Ldα-SNAPs have retained ancestral functions through subfunctionalization, and subsequently, they acquired parasite-specific neofunction(s) through the accumulation of natural mutation(s).

01 Jan 2025·American Journal of Ophthalmology

Nonredundant Role of Leishmanolysin-Like (Lmln) Zinc-Metallopeptidase in Retinal Homeostasis

Article

Author: Zegeye, Yeshumenesh ; Ludwig, Sara ; Shrestha, Sangita ; Moresco, Eva Marie Y. ; Ufret-Vincenty, Rafael L. ; Yuksel, Seher ; Ulker-Yilmazer, Gizem ; He, Yu-Guang ; Kirman, Dogan Can ; Beutler, Bruce ; Moresco, Eva Marie Y ; Ufret-Vincenty, Rafael L ; Aredo, Bogale ; Turpin, Emily

PURPOSETo determine if Lmln, a Zinc-metallopeptidase, is important for retinal homeostasis.DESIGNBasic research in mouse models of retinal degeneration.METHODSCombining an unbiased N-ethyl-N-nitrosourea mutagenesis pipeline in mice with optical coherence tomography (OCT) screening and automated meiotic mapping, we identified an allele (nemeth) that seemed to be associated with outer nuclear layer (ONL) thinning. Since nemeth was predicted to lead to a nonsense mutation of the Lmln gene, we targeted Lmln using CRISPR/Cas-9 technology and characterized the impact on retinal anatomy and function.RESULTSOCT imaging demonstrated an outer retinal degeneration in Lmln^-/- mice (P = 7.3 × 10^-9 for ONL at 2 m) that progressed over the first 6 months of life and then stabilized. Light microscopy showed loss of ONL nuclei (P ranged between .00033 and .0097 for posterior measurements), and a TUNEL assay revealed a small but significant increase in apoptosis (P = .034). Lmln^-/- mice accumulated fundus spots (P = .0030 by 2 m of age) and activated subretinal microglia (P ranged from .0007 to 8 × 10^-13 for Gal3⁺ cells). Scotopic electroretinography demonstrated a decrease in retinal function in Lmln^-/- mice both at 6 m (only a-wave, P < .01 for all stimuli) and at 10 m of age (P < .01 for both a-wave and b-wave with all stimuli).CONCLUSIONSOur work revealed a previously unknown essential role for Lmln in maintaining retinal anatomy and function. Further studies using this new model will be aimed at determining the cellular expression of Lmln and its mechanisms of action within the retina.

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LMLN

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