Nova pesquisa aponta a proteína PTP1B como candidato promissor para retardar a progressão do Alzheimer em pacientes

Genetically encoded biosensors are powerful tools for linking metabolite production to fluorescent outputs, but stresses imposed by engineered pathways can confound their signals. In this study, we developed four fluorescence-based biosensors for inhibitors of protein tyrosine phosphatase 1B (PTP1B), a therapeutic target for cancer and diabetes, and compared their performance in the presence of heterologous terpenoid pathways, a promising source of new inhibitors. When expressed in Escherichia coli, all four could reliably detect an exogenously supplied PTP1B inhibitor, but only one remained functional alongside terpenoid pathways, where pathway-derived stress reduced overall fluorescence. This sensor, which links PTP1B inhibition to the assembly of a split T7 RNA polymerase, exhibited a high dynamic range with minimal toxicity, a common liability of T7-based circuits. Variants of this sensor with different sensitivities to inhibition and stress allowed us to separate the terpenoid pathways that made PTP1B inhibitors from those that did not. Our findings show how pathway-specific stresses (e.g., terpene synthase expression) can alter biosensor signals as strongly as their target analytes and provide a framework for disentangling these confounding effects in high-throughput screens.

Researchers have identified a new potential weapon against Alzheimer’s: blocking a protein called PTP1B. In mice, this approach boosted memory and helped brain immune cells clear harmful plaque buildu...

Shutting down the enzyme PTP1B helps brain immune cells clear plaques again, pointing to a potential new Alzheimer’s treatment approach.

The absence of a phosphatase prevents a cardiomyopathy-inducing metabolic switch in mice on a high-fat diet.

Researchers have identified a new potential weapon against Alzheimer’s: blocking a protein called PTP1B. In mice, this approach boosted memory and helped brain immune cells clear harmful plaque buildu...

Forscher am Cold Spring Harbor Laboratory haben ein Protein entdeckt, dessen Hemmung bei Alzheimermäusen das Gedächtnis auf das Niveau gesunder Tiere bringt und die Plaqueablagerungen im Gehirn reduziert.

Protein tyrosine phosphorylation is critical for cellular function, and aberrant phosphorylation is tied to a wide range of human diseases. Identifying the substrates of protein tyrosine phosphatases,...

The rapid identification of protein–protein interactions has been significantly enabled by mass spectrometry (MS) proteomics-based methods, including affinity purification-MS, crosslinking-MS, and pr...

【J Ethnopharmacol】<AbstractText Label="ETHNOPHARMACOLOGICAL RELEVANCE" NlmCategory="BACKGROUND">Ziziphus jujuba Mill. var. spin...

Researchers have identified a new potential weapon against Alzheimer’s: blocking a protein called PTP1B. In mice, this approach boosted memory and helped brain immune cells clear harmful plaque buildu...

Shutting down the enzyme PTP1B helps brain immune cells clear plaques again, pointing to a potential new Alzheimer’s treatment approach.

يعمل الباحثون في مختبر "كولد سبرينج هاربور"، وهو معهد غير ربحي مقره ولاية نيويورك، على تطوير علاجات جديدة محتملة لتثبيط إنزيم "PTP1B"، الذي قد يسهم في فقدان

Read the full paper: PTP1B deficiency in the reward system suppressed the rewarding value of a high-fat diet

Mounting evidence implicates pathogen infections in the pathogenesis of Alzheimer&#8217;s disease (AD), yet the cellular mechanisms underlying infection-induced neurodegeneration remain poorly understood. Central to this process is the dysfunction of astrocyte-neuron interactions, which are critical for maintaining neuroinflammatory balance and synaptic homeostasis. Here, we demonstrate that astrocytic protein tyrosine phosphatase 1B (PTP1B) acts as a key regulator of astrocyte reactivity during infection, leading to impaired neuroglial communications and cognitive decline. In a murine model of chronic Toxoplasma gondii (T. gondii) infection, elevated PTP1B levels in astrocytes were closely associated with neuroinflammation and cognitive impairments. Conditional deletion of astrocytic PTP1B or its pharmacological inhibition mitigated neuroinflammation, restored synaptic integrity, and rescued cognitive function. Mechanistically, astrocytic PTP1B induced the polarization of A1-like neur

Read the full paper: Ganaxolone, an approved therapy for CDKL5-Deficiency Disorder, is an inhibitor of PTP1B

Background Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown. Methods To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absen