Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models DOI Creative Commons
Kathrine L. Jensen, Nikolaj Riis Christensen,

Carolyn Marie Goddard

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(20)

Published: Sept. 17, 2024

Chronic pain is a complex, debilitating, and escalating health problem worldwide, impacting 1 in 5 adults. Current treatment compromised by dose-limiting side effects, including high abuse liability, loss of ability to function socially professionally, fatigue, drowsiness, apathy. PICK1 has emerged as promising target for the chronic conditions. Here, we developed characterized cell-permeable fatty acid-conjugated bivalent peptide inhibitor assessed its effects on acute pain. The myristoylated inhibitor, myr-NPEG4-(HWLKV)2 (mPD5), self-assembled into core-shell micelles that provided favorable pharmacodynamic properties relieved evoked mechanical thermal hypersensitivity well ongoing anxiodepressive symptoms mouse models neuropathic inflammatory following subcutaneous administration. No overt were associated with mPD5 administration, it had no effect nociception. Finally, was far phase (18 weeks after spared nerve injury surgery) while single injection ceased few hours, repeated administration relief lasting up 20 hours last injection.

Language: Английский

Divergent roles of functional foods on anthropometric indices and gut microbiota in overweight and obese individuals: Insilico approaches and multi-omics insights DOI Creative Commons

Oladayo Emmanuel Apalowo,

Isaac Duah Boateng

Trends in Food Science & Technology, Journal Year: 2025, Volume and Issue: unknown, P. 104876 - 104876

Published: Jan. 1, 2025

Language: Английский

Citations

1
mPD5, a peripherally restricted PICK1 inhibitor for treating chronic pain DOI
Kathrine L. Jensen,

Nikolaj Riis Chistensen,

Carolyn Marie Goddard

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: March 3, 2023

ABSTRACT Chronic pain is a complex, debilitating, and escalating health problem worldwide, impacting one in five adults. Current treatment compromised by dose-limiting side effects including high abuse liability, loss of ability to function socially professionally, fatigue, drowsiness, apathy. PICK1 has emerged as promising target for the chronic conditions. Here, we develop characterize cell-permeable fatty acid conjugated bivalent peptide inhibitor assess its on acute pain. The myristoylated myr-NPEG 4 -(HWLKV) 2 , (mPD5), self-assembles into core-shell micelles that provide favourable pharmacodynamic properties relieves ongoing evoked mechanical hypersensitivity, thermal hypersensitivity well anxio-depressive symptoms mouse models neuropathic inflammatory following subcutaneous administration. No overt no were associated with mPD5 administration, it effect nociception. Finally, relieved far phase (18 weeks post SNI surgery) while single injection ceases after few hours, repeated administration provides relief lasting up 20 hours last injection.

Language: Английский

Citations

1
Central leptin signaling deficiency induced by leptin receptor antagonist leads to hypothalamic proteomic remodeling DOI Creative Commons
Lorena Mazuecos, Sara Artigas-Jerónimo, Cristina Pintado

et al.

Life Sciences, Journal Year: 2024, Volume and Issue: 346, P. 122649 - 122649

Published: April 16, 2024

Leptin irresponsiveness, which is often associated with obesity, can have significant impacts on the hypothalamic proteome of individuals, including those who are lean. While mounting evidence leptin irresponsiveness has focused obese understanding early molecular and proteomic changes deficient signaling in lean individuals essential for intervention prevention metabolic disorders. receptor antagonists block binding to its receptors, potentially reducing effects used cases where excessive activity might be harmful. In this work, we blocked central actions male adult Wistar rat by chronically administering intracerebroventricularly superactive antagonist (SLA) (D23L/L39A/D40A/F41A) investigated impact using label-free sequential window acquisition all theoretical fragment ion spectra mass spectrometry (SWATH-MS) quantitative proteomics. Our results show an accumulation proteins involved mRNA processing, stability, translation hypothalamus SLA-treated rats. Conversely, deficiency reduces representation implicated energy metabolism, neural circuitry, neurotransmitter release. The alterations contribute dysregulate appetite, balance, key factors development progression obesity related Additionally, bioinformatic analysis, identified a series transcription that upstream regulatory mechanisms responsible observed signature.

Language: Английский

Citations

0
Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models DOI Creative Commons
Kathrine L. Jensen, Nikolaj Riis Christensen,

Carolyn Marie Goddard

et al.

JCI Insight, Journal Year: 2024, Volume and Issue: 9(20)

Published: Sept. 17, 2024

Chronic pain is a complex, debilitating, and escalating health problem worldwide, impacting 1 in 5 adults. Current treatment compromised by dose-limiting side effects, including high abuse liability, loss of ability to function socially professionally, fatigue, drowsiness, apathy. PICK1 has emerged as promising target for the chronic conditions. Here, we developed characterized cell-permeable fatty acid-conjugated bivalent peptide inhibitor assessed its effects on acute pain. The myristoylated inhibitor, myr-NPEG4-(HWLKV)2 (mPD5), self-assembled into core-shell micelles that provided favorable pharmacodynamic properties relieved evoked mechanical thermal hypersensitivity well ongoing anxiodepressive symptoms mouse models neuropathic inflammatory following subcutaneous administration. No overt were associated with mPD5 administration, it had no effect nociception. Finally, was far phase (18 weeks after spared nerve injury surgery) while single injection ceased few hours, repeated administration relief lasting up 20 hours last injection.

Language: Английский

Citations

0