Renin-Angiotensin System Impacts on Dopaminergic Neurodegeneration
Summary
The renin–angiotensin system (RAS), long recognised for its role in cardiovascular regulation, exists as a local paracrine network within the brain, where it exerts profound effects on dopaminergic neurons. In the nigrostriatal pathway, interactions between dopamine and angiotensin II determine a balance between neuronal survival and degeneration. Overactivation of angiotensin II type 1 receptors (AT1) in neurons and microglia enhances NADPH-oxidase-derived reactive oxygen species, intracellular calcium dysregulation, neuroinflammatory signalling and α-synuclein aggregation. These events converge on oxidative stress, microglial M1 polarisation and blood–brain barrier compromise, accelerating dopaminergic cell loss characteristic of Parkinson’s disease. An opposing arm of RAS, mediated by angiotensin II type 2 and Mas receptors, promotes anti-oxidative and anti-inflammatory pathways, offering intrinsic neuroprotection. Dysregulation towards the pro-oxidative AT1 axis has been documented in animal models of ageing, hormonal decline and genetic vulnerability. Moreover, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors further amplify neuroinflammation and barrier leakage. Modulation of brain RAS through AT1 receptor blockers, enhancement of the protective axis or targeting of pathological autoantibodies emerges as a promising strategy to slow dopaminergic neurodegeneration and to improve outcomes for patients at prodromal and early stages of Parkinson’s disease.
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Renin-Angiotensin System Impacts on Dopaminergic Neurodegeneration publication trend
The graph below shows the total number of articles in renin-angiotensin system impacts on dopaminergic neurodegeneration across all publications each year (not limited to Nature Index journals).
Technical terms
Renin–Angiotensin System (RAS): Hormonal cascade regulating blood pressure and local tissue functions via angiotensin peptides and receptors.
Angiotensin II Type 1 Receptor (AT1 receptor): Cell-surface receptor mediating pro-oxidative, pro-inflammatory actions of angiotensin II.
Dopaminergic Neurons: Neurons producing dopamine, critical for motor control and vulnerable in Parkinson’s disease.
NADPH Oxidase: Enzyme complex generating reactive oxygen species, implicated in neuronal oxidative stress.
α-Synuclein: Neuronal protein prone to aggregation, central to the pathogenesis of synucleinopathies.
Microglial Polarization: Phenotypic shift of microglia towards pro-inflammatory (M1) or anti-inflammatory (M2) states.
Autoantibodies against AT1 receptors: Immunoglobulins targeting AT1 that act as receptor agonists and disrupt blood–brain barrier integrity.
References
- The role of the brain renin-angiotensin system in Parkinson´s disease. Translational Neurodegeneration (2024).
- Angiotensin type 1 receptor activation promotes neuronal and glial alpha-synuclein aggregation and transmission. npj Parkinson's Disease (2024).
- Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson’s disease models. Stem Cell Research & Therapy (2024).
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