Retinoid X Receptor as a Novel Drug Target to Treat Neurological Disorders Associated with α- Synucleinopathies DOI Creative Commons
Assylbek Zhylkibayev, Christopher R. Starr, M. Iqbal Hossain

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

This study investigated the therapeutic potential of nuclear retinoid X receptor (RXR) in mitigating progression alpha-synucleinopathies (αSNPs), particularly Parkinson's disease (PD). PD-like pathology mice was successfully induced through co-delivery AAV expressing human α-synuclein (αS) and αS preformed fibrils (PFFs) into substantia nigra pars compacta (SNpc). Significant increases Lewy body (LB)-like inclusions, loss tyrosine hydroxylase-positive (TH+) neurons, reductions dopamine (DA) levels striatum were observed. Additionally, diminished PPARα NURR1, along with elevated GFAP Iba1, markers neuroinflammation, microglial activation, astrocytic gliosis associated PD pathogenesis. AAV-mediated overexpression RXRα demonstrated preservation TH+ prevention DA decline attenuation accumulation. Furthermore, RXR-treated brains showed a reduced number GFAP+ Iba1+ cells, decreased immunoreactivity, fewer less widespread LB-like aggregates. RXR also enhanced production proteins critical for neuronal survival. These findings suggest that activation promotes neuroprotection by αSNPs chronic major contributor to progression. research underscores targeting receptors, such as RXR, neurodegenerative diseases like PD.

Language: Английский

Imaging Alpha-synuclein with Novel 5H-Imidazo[1,5-b][1,2,4]triazole Radioligands for the Diagnosis of Parkinson’s Disease DOI Creative Commons
Zhendong Song, Steven H. Liang

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(2), P. 182 - 183

Published: Jan. 6, 2025

The invention in this patent describes novel 5H-imidazo[1,5-b][1,2,4]triazole compounds, including radiolabeled derivatives, designed to target alpha-synuclein (α-syn). These compounds demonstrate potential as positron emission tomography (PET) radioligands for diagnosing α-syn-associated brain diseases, Parkinson's disease.

Language: Английский

Citations

0
Retinoid X Receptor as a Novel Drug Target to Treat Neurological Disorders Associated with α- Synucleinopathies DOI Creative Commons
Assylbek Zhylkibayev, Christopher R. Starr, M. Iqbal Hossain

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

This study investigated the therapeutic potential of nuclear retinoid X receptor (RXR) in mitigating progression alpha-synucleinopathies (αSNPs), particularly Parkinson's disease (PD). PD-like pathology mice was successfully induced through co-delivery AAV expressing human α-synuclein (αS) and αS preformed fibrils (PFFs) into substantia nigra pars compacta (SNpc). Significant increases Lewy body (LB)-like inclusions, loss tyrosine hydroxylase-positive (TH+) neurons, reductions dopamine (DA) levels striatum were observed. Additionally, diminished PPARα NURR1, along with elevated GFAP Iba1, markers neuroinflammation, microglial activation, astrocytic gliosis associated PD pathogenesis. AAV-mediated overexpression RXRα demonstrated preservation TH+ prevention DA decline attenuation accumulation. Furthermore, RXR-treated brains showed a reduced number GFAP+ Iba1+ cells, decreased immunoreactivity, fewer less widespread LB-like aggregates. RXR also enhanced production proteins critical for neuronal survival. These findings suggest that activation promotes neuroprotection by αSNPs chronic major contributor to progression. research underscores targeting receptors, such as RXR, neurodegenerative diseases like PD.

Language: Английский

Citations

0