The Renin–Angiotensin System Modulates Dopaminergic Neurotransmission: A New Player on the Scene

Abstract

Parkinson’s disease (PD) is an extrapyramidal disorder characterized by neuronal degeneration in several regions of the peripheral and central nervous systems. It is the second most frequent neurodegenerative disease after Alzheimer’s. It has become a major health problem, affecting 1% of the world population over 60 years old and 3% of people beyond 80 years. The main histological findings are intracellular Lewy bodies composed of misfolded α-synuclein protein aggregates and loss of dopaminergic neurons in the central nervous system. Neuroinflammation, apoptosis, mitochondrial dysfunction, altered calcium homeostasis, abnormal protein degradation, and synaptic pathobiology have been put forward as mechanisms leading to cell death, α-synuclein deposition, or both. A progressive loss of dopaminergic neurons in the substantia nigra late in the neurodegeneration leads to developing motor symptoms like bradykinesia, tremor, and rigidity. The renin–angiotensin system (RAS), which is involved in regulating blood pressure and body fluid balance, also plays other important functions in the brain. The RAS is involved in the autocrine and paracrine regulation of the nigrostriatal dopaminergic synapses. Dopamine depletion, as in PD, increases angiotensin II expression, which stimulates or inhibits dopamine synthesis and is released via AT1 or AT2 receptors. Furthermore, angiotensin II AT1 receptors inhibit D1 receptor activation allosterically. Therefore, the RAS may have an important modulating role in the flow of information from the brain cortex to the basal ganglia. High angiotensin II levels might even aggravate neurodegeneration, activating the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, which leads to increased reactive oxygen species production.

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

“…High levels of angiotensin II may enhance neurodegeneration by activating the NADPH oxidase complex, which leads to increased production of reactive oxygen species. 210 The manipulation of the RAAS, leading to an increase in the expression of ACE2, can affect endocrine functions, which can play an important role in pathological processes. 201 In addition, ACE2 in the intestine functions as a partner for the amino acid transporter B0AT1.…”

Identifying Protective Drugs for Parkinson's Disease in Health‐Care Databases Using Machine Learning

“…It is possible that age‐related BBB alterations or high doses may facilitate its penetration into the brain 29 . Alternatively, whether peripheral changes in body fluid homeostasis due to furosemide have central effects remains to be determined 30,31 …”

Recent developments in the probiotics as live biotherapeutic products (LBPs) as modulators of gut brain axis related neurological conditions

“…Angiotensin II is a pro-inflammatory peptide that can activate the NADPH-dependent oxidase complex, causing the formation of ROS, which may lead to the death of dopaminergic cells [ 133 ]. AT 1 and AT 2 receptors were associated with dopaminergic system [ 134 ]. Angiotensin converting enzyme activity and Angiotensin II levels were elevated by dopamin degeneration.…”