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Renin-Angiotensin System in Huntington's Disease: Evidence from Animal Models and Human Patients
Lucas M Kangussu1, Natalia P Rocha2,3,4, Priscila A C Valadão1
1Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
International Journal of Molecular Sciences
|July 27, 2022
Summary
An imbalance in the brain Renin-Angiotensin System (RAS) may contribute to Huntington's disease (HD) progression. This study found altered RAS components in HD mice and patients, suggesting a potential therapeutic target.
Area of Science:
- Neuroscience
- Endocrinology
- Genetics
Background:
- The Renin-Angiotensin System (RAS) is present in the brain and influences neurological functions.
- Dysregulation of brain RAS is implicated in neurodegenerative diseases.
- The role of RAS in Huntington's disease (HD) pathophysiology remains largely unexplored.
Purpose of the Study:
- To investigate the involvement of both classical and alternative axes of the RAS in Huntington's disease (HD).
- To analyze RAS component alterations in a mouse model of HD and in human HD patient samples.
Main Methods:
- Utilized the BACHD mouse model for Huntington's disease (HD).
- Examined motor performance in behavioral tests.
- Quantified levels and activity of RAS components (ACE, ACE2, Ang II, Ang-(1-7), Mas receptors, AT1 receptor) in brain regions and plasma.
- Analyzed mRNA expression of AT1 receptor in key brain areas.
Main Results:
- BACHD mice showed impaired motor function.
- A decrease in alternative RAS axis components (ACE2, Ang-(1-7), Mas receptors) was observed in BACHD mouse brains.
- Increased AT1 receptor mRNA expression, a component of the classical RAS arm, was found in key brain regions of BACHD mice.
- HD patients exhibited elevated plasma Ang-(1-7) levels.
Conclusions:
- The study provides the first evidence for an imbalance between the classical and counter-regulatory arms of the RAS in Huntington's disease (HD) pathophysiology.
- Alterations in brain RAS components suggest a potential role in HD progression.
- The findings highlight the RAS as a potential therapeutic target for HD.
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