31 May 2018 : Animal Research
A Possible Role for Long Interspersed Nuclear Elements-1 (LINE-1) in Huntington’s Disease ProgressionHuiping Tan1ABCDEFG, Chunlin Wu2ABCDE, Lei Jin1ACDEF*
Med Sci Monit 2018; 24: ANS3644-3652
BACKGROUND: Recent studies have shown that increased mobilization of Long Interspersed Nuclear Elements-1 (L1) can promote the pathophysiology of multiple neurological diseases. However, its role in Huntington’s disease (HD) remains unknown.
MATERIAL AND METHODS: R6/2 mice – a common mouse model of HD – were used to evaluate changes in L1 mobilization. Pyrosequencing was used to evaluate methylation content changes. L1-ORF1 and L1-ORF2 expression analysis were evaluated by RT-PCR and immunoblotting. Changes in pro-survival signaling were evaluated by L1-ORF overexpression studies and validated in the mouse model by immunohistochemistry and immunoblotting.
RESULTS: We found an increased mobilization of L1 elements in the caudate genome of R6/2 mice (p<0.05) – a common mouse model of HD – but not in wild-type mice. Subsequent pyrosequencing and expression analysis showed that the L1 elements were hypomethylated and their respective ORFs were overexpressed in the affected tissues. In addition, a significant decrease in the pro-survival proteins such as the phosphoproteins of AKT target proteins, mTORC1 activity, and AMPK alpha levels was observed with the increase in the expression L1-ORF2.
CONCLUSIONS: These findings indicate that hyperactive retrotransposition of L1 triggers a downstream signaling pathway affecting the neuronal survival pathways via downregulation of mTORC1 activity and AMPKalpha and increasing apoptosis in neurons.
Keywords: AMP-Activated Protein Kinases, Long Interspersed Nuclear Elements-1, Huntington’s disease
01 December 2021 : EditorialEditorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19
Med Sci Monit 2022; 28:e937048
04 May 2022 : Clinical ResearchEffects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936069
22 April 2022 : Clinical ResearchFactors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)
Med Sci Monit In Press; DOI: 10.12659/MSM.936547
27 April 2022 : Meta-AnalysisEffect of the COVID-19 Pandemic on Serum Vitamin D Levels in People Under Age 18 Years: A Systematic Review...
Med Sci Monit In Press; DOI: 10.12659/MSM.935823
20 May 2022 : Clinical ResearchEfficacy of Focused Extracorporeal Shock Wave Therapy in Chronic Low Back Pain: A Prospective Randomized 3-...
Med Sci Monit In Press; DOI: 10.12659/MSM.936614
19 May 2022 : Clinical ResearchAssociation Between Serum Homocysteine Levels and Severity of Diabetic Kidney Disease in 489 Patients with ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936323
18 May 2022 : Clinical ResearchPhysical and Psychosocial Concept Domains Related to Health-Related Quality of Life (HRQL) in 50 Girls and ...
Med Sci Monit In Press; DOI: 10.12659/MSM.936801
Most Viewed Current Articles
31 Dec 1969 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
31 Dec 1969 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292
31 Dec 1969 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996