دورية أكاديمية
Low-dose radiation decreases Lrrk2 levels in the striatum of large mammalian brains: New venues to treat Parkinson's disease?
| العنوان: | Low-dose radiation decreases Lrrk2 levels in the striatum of large mammalian brains: New venues to treat Parkinson's disease? |
|---|---|
| المؤلفون: | Iacono D; DoD/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA; Department of Neurology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA; Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA; Neuroscience Program, Department of Anatomy, Physiology & Genetics, Uniformed Services University (USU), Bethesda, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD, USA. Electronic address: diego.iacono.ctr@usuhs.edu., Murphy EK; DoD/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD, USA., Stimpson CD; DoD/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA; The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD, USA., Perl DP; DoD/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD, USA; Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA., Day RM; Department of Pharmacology and Molecular Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University (USU), Bethesda, MD, USA. |
| المصدر: | Parkinsonism & related disorders [Parkinsonism Relat Disord] 2024 Jul; Vol. 124, pp. 107024. Date of Electronic Publication: 2024 Jun 02. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 9513583 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5126 (Electronic) Linking ISSN: 13538020 NLM ISO Abbreviation: Parkinsonism Relat Disord Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Kidlington, Oxford, U.K. ; Tarrytown, NY : Elsevier Science, c1995- |
| مواضيع طبية MeSH: | Leucine-Rich Repeat Serine-Threonine Protein Kinase-2*/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2*/metabolism , Parkinson Disease*/metabolism , Parkinson Disease*/genetics, Animals ; Female ; Male ; alpha-Synuclein/metabolism ; Corpus Striatum/metabolism ; Corpus Striatum/radiation effects ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Swine ; Tyrosine 3-Monooxygenase/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism |
| مستخلص: | Introduction: Among gene mutations and variants linked to an increased risk of PD, mutations of leucine-rich repeat kinase 2 gene (LRRK2) are among the most frequently associated with early- and late-onset PD. Clinical and neuropathological characteristics of idiopathic-PD (iPD) and LRRK2-PD are similar, and these similarities suggest that the pathomechanisms between these two conditions are shared. LRRK2 mutations determine a gain-of-function and yield higher levels of lrrk2 across body tissues, including brain. On another side, recent animal studies supported the potential use of low dose radiation (LDR) to modify the pathomechanisms of diseases such as Alzheimer's disease (AD). Methods: We assessed if a single total-body LDR (sLDR) exposure in normal swine could alter expression levels of the following PD-associated molecules: alpha-synuclein (α-syn), phosphorylated-α-synuclein (pα-syn), parkin, tyrosine hydroxylase (th), lrrk2, phosphorylated-lrrk2 (pS935-lrrk2), and some LRRK2 substrates (Rab8a, Rab12) across different brain regions. These proteins were measured in frontal cortex, hippocampus, striatum, thalamus/hypothalamus, and cerebellum of 9 radiated (RAD) vs. 6 sham (SH) swine after 28 days from a sLDR of 1.79Gy exposure. Results: Western Blot analyses showed lowered lrrk2 levels in the striatum of RAD vs. SH swine (p < 0.05), with no differences across the remaining brain regions. None of the other protein levels differed between RAD and SH swine in any examined brain regions. No lrrk2 and p-lrrk2 (S935) levels differed in the lungs of RAD vs. SH swine. Conclusions: These findings show a specific striatal lrrk2 lowering effect due to LDR and support the potential use of LDR to interfere with the pathomechanisms of PD. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| فهرسة مساهمة: | Keywords: LRRK2; Low dose radiation; Parkinson's disease; Striatum |
| المشرفين على المادة: | 0 (alpha-Synuclein) EC 2.7.11.1 (Leucine-Rich Repeat Serine-Threonine Protein Kinase-2) EC 2.3.2.27 (parkin protein) EC 2.7.11.1 (Protein Serine-Threonine Kinases) EC 1.14.16.2 (Tyrosine 3-Monooxygenase) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20240606 Date Completed: 20240703 Latest Revision: 20240729 |
| رمز التحديث: | 20240729 |
| DOI: | 10.1016/j.parkreldis.2024.107024 |
| PMID: | 38843617 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1873-5126 |
|---|---|
| DOI: | 10.1016/j.parkreldis.2024.107024 |