Wang 2024 J Biomed Sci

From Bioblast
Publications in the MiPMap
Wang V, Tseng KY, Kuo TT, Huang EY, Lan KL, Chen ZR, Ma KH, Greig NH, Jung J, Choi HI, Olson L, Hoffer BJ, Chen YH (2024) Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice. J Biomed Sci 31:38. https://doi.org/10.1186/s12929-024-01025-6

Β» PMID: 38627765 Open Access

Wang Vicki, Tseng Kuan-Yin, Kuo Tung-Tai, Huang Eagle Yi-Kung, Lan Kuo-Lun, Chen Zi-Rong, Ma Kuo-Hsing, Greig Nigel H, Jung Jin, Choi Ho-li, Olson Lars, Hoffer Barry J, Chen Yuan-Hao (2024) J Biomed Sci

Abstract: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood.

In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse.

Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae.

Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD. β€’ Keywords: Exenatide, Glucagon-like peptide-1 receptor agonist, MitoPark mouse, Mitochondria, PT320, Parkinson’s disease β€’ Bioblast editor: Plangger M


Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Parkinson's 

Organism: Mouse  Tissue;cell: Nervous system  Preparation: Homogenate 


Coupling state: ET, LEAK, OXPHOS  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2024-07 

Cookies help us deliver our services. By using our services, you agree to our use of cookies.