Genetically modified E. Coli secreting melanin (E.melanin) activates the astrocytic PSAP-GPR37L1 pathway and mitigates the pathogenesis of Parkinson’s disease DOI Creative Commons

Weixian Kong,

Yu Liu,

Pu Ai

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 10, 2024

The characteristic neuropathology of Parkinson's disease (PD) involves the abnormal accumulation phosphorylated α-synuclein (αSyn), as well a significant decrease in neuromelanin (NM) levels within dopamine neurons (DaNs). Unlike αSyn aggregates, relationship between NM and PD pathogenesis is not understood. In this study, we engineered an E. coli MG1655 strain to produce exosomes containing melanin (E.melanin), investigated its potential neuroprotective effects on DaNs context PD. By employing combination cell cultures, biochemical studies, single nuclear RNA sequencing (snRNA seq), various vivo validations, found that administration E.melanin effectively alleviated loss improved motor behavior impairments observed both pharmacological transgenic mouse models. Mechanistically, snRNA seq data suggested activated PSAP-GPR37L1 signaling pathway specifically astrocytes, leading reduction astrocytic engulfment synapses. Notably, activation GPR37L1 receptor using Tx14(A) peptide successfully rescued defects protected against degeneration mice with Overall, our findings provide novel insights into understanding molecular mechanisms underlying melanin's protective while offering strategies for manipulating treating pathophysiological progression.

Language: Английский

Genetically Designed Living Bacteria with Melanogenesis for Tumor‐Specific Pigmentation and Therapeutic Intervention DOI Creative Commons
Liying Wang, Qi Wu,

Qi Lyu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 18, 2024

Abstract Visual observation and therapeutic intervention against tumors hold significant appeal for tumor treatment, particularly in meeting the demands of intraoperative navigation. From a clinical perspective, naked‐eye visualization provides direct convenient approach to identifying navigating during surgery. Nevertheless, there is an ongoing need develop effective solutions this frontier. Genetically engineered microorganisms are promising as living therapeutics combatting malignant tumors, leveraging precise targeting versatile programmed functionalities. Here, genetically modified Escherichia coli ( E. ) MG1655 bacterial cells introduced, called MelaBac cells, designed express tyrosinase continuously. This bioengineered melanogenesis produces melanin capable pigmenting both subcutaneous CT26 xenografts chemically induced colorectal cancer (CRC). Additionally, demonstrate initiation photonic hyperthermia therapy immunotherapy offering selective interventions with high biocompatibility.

Language: Английский

Citations

4
Metabolic Reprogramming of Tumor Microenviroment by Engineered Bacteria DOI
Heng Wang, Fang Xu, Chao Wang

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Tyrosinases: a family of copper-containing metalloenzymes DOI Creative Commons
Matthias Pretzler, Annette Rompel

ChemTexts, Journal Year: 2024, Volume and Issue: 10(4)

Published: Nov. 30, 2024

Abstract Tyrosinases (TYRs) are a family of copper-containing metalloenzymes that present in all domains life. TYRs catalyze the reactions start biosynthesis melanin, main pigment animal kingdom, and also involved formation bright colors seen on caps mushrooms petals flowers. ortho -hydroxylation oxidation phenols catechols to respective o -quinones. They only need molecular oxygen do that, products TYRs— -quinones—are highly reactive will usually react with next available nucleophile. This reactivity can be harnessed for pharmaceutical applications as well environmental food biotechnology. The majority both basic applied research utilizes “mushroom tyrosinase”, crude enzyme preparation derived from button mushroom ( Agaricus bisporus ) fruiting bodies. Access pure TYR preparations comes almost exclusively production recombinant purification these enzymes natural source is very laborious plagued by low yields. In this text an introduction into biochemistry given, followed overview structural data TYRs, current model catalytic mechanism, survey reports important metalloenzyme family, review synthesis catechols, biosensors, bioremediation, cross-linking proteins medical hydrogels melanoma treatment. Graphical

Language: Английский

Citations

3
Genetically modified E. Coli secreting melanin (E.melanin) activates the astrocytic PSAP-GPR37L1 pathway and mitigates the pathogenesis of Parkinson’s disease DOI Creative Commons

Weixian Kong,

Yu Liu,

Pu Ai

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 10, 2024

The characteristic neuropathology of Parkinson's disease (PD) involves the abnormal accumulation phosphorylated α-synuclein (αSyn), as well a significant decrease in neuromelanin (NM) levels within dopamine neurons (DaNs). Unlike αSyn aggregates, relationship between NM and PD pathogenesis is not understood. In this study, we engineered an E. coli MG1655 strain to produce exosomes containing melanin (E.melanin), investigated its potential neuroprotective effects on DaNs context PD. By employing combination cell cultures, biochemical studies, single nuclear RNA sequencing (snRNA seq), various vivo validations, found that administration E.melanin effectively alleviated loss improved motor behavior impairments observed both pharmacological transgenic mouse models. Mechanistically, snRNA seq data suggested activated PSAP-GPR37L1 signaling pathway specifically astrocytes, leading reduction astrocytic engulfment synapses. Notably, activation GPR37L1 receptor using Tx14(A) peptide successfully rescued defects protected against degeneration mice with Overall, our findings provide novel insights into understanding molecular mechanisms underlying melanin's protective while offering strategies for manipulating treating pathophysiological progression.

Language: Английский

Citations

2