Unlocking ACE2’s role in COVID-19 induced neurological disorders

Medical News: In recent years, ACE2, or angiotensin-converting enzyme 2, has emerged as a pivotal player in neuroscience, especially as the COVID-19 pandemic has intensified focus on this enzyme’s role in neurological health. The research team, including experts from Henan University’s Institute for Brain Sciences Research and the Institute for Sports and Brain Health in Kaifeng, China, delved into ACE2’s function in the nervous system, its impact on neurodegenerative diseases, and its relationship with COVID-19. This Medical News report explores the findings of this significant study, shedding light on how ACE2 operates within the brain and how COVID-19 disrupts its normal functions, leading to a range of neurological disorders.


Unlocking ACE2’s role in COVID-19 induced neurological disorders

What is ACE2?
ACE2 is a multifunctional enzyme, best known for its role in regulating blood pressure by balancing the renin-angiotensin system (RAS). It serves dual purposes - acting as a receptor for viruses like SARS-CoV-2 and playing a vital role in protecting brain cells. Researchers have long known that ACE2 helps maintain the body’s vascular systems, but its importance in brain function is becoming clearer.
 
ACE2 and the Brain: A Complex Relationship
ACE2 is present in various regions of the brain, including neurons and glial cells, as well as parts of the brainstem, hippocampus, and other areas responsible for cognitive functions and emotion regulation. These discoveries emphasize that ACE2 is integral to brain health, involved in activities like neurotransmitter release, inflammation control, and blood-brain barrier (BBB) integrity. In Alzheimer's disease (AD), Parkinson’s disease (PD), ischemic stroke (IS), and even conditions like anxiety and depression, ACE2 appears to be a key regulator of neurological homeostasis.
 
The study explores how ACE2 expression in these key regions of the brain affects neurological outcomes. For instance, ACE2 reduces inflammation and oxidative stress, two factors that are often involved in brain disorders. It also plays a role in repairing the brain by promoting neurogenesis and stabilizing the BBB, preventing harmful substances from entering the brain.
 
Impact of COVID-19 on ACE2 and the Nervous System
COVID-19 has highlighted the complex role of ACE2 in the nervous system. The virus enters human cells by binding to ACE2, found on the surface of cells in many organs, including the lungs and the brain. This interaction disrupts ACE2's normal protective functions, leading to neurological symptoms in COVID-19 patients. These include headaches, dizziness, loss of smell and taste, and more severe conditions like strokes and encephalitis.
 
One of the critical ways that SARS-CoV-2 disrupts ACE2 function is by altering the balance between two key components of the RAS - angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7). Under normal conditions, ACE2 converts the pro-inflammatory Ang II into Ang 1-7, which has protective, anti-inflammatory properties. However, when SARS-CoV-2 binds to ACE2, it prevents this conversion, leading to elevated levels of Ang II. This can result in increased inflammation, oxidative stress, and even damage to neurons.
 
Key Study Findings: ACE2’s Role in Neurological Disorders
-Alzheimer’s Disease (AD): ACE2 levels are lower in patients with AD, especially in brain areas critical for memory and cognition, such as the hippocampus and frontal cortex. ACE2’s ability to reduce the buildup of amyloid-beta (Aβ) proteins and neurofibrillary tangles, both hallmarks of AD, positions it as a promising therapeutic target. Treatments that increase ACE2 expression, such as the drug DIZE, have been shown to improve cognitive function in animal models of AD.
 
-Parkinson’s Disease (PD): Elevated levels of ACE2 autoantibodies have been observed in patients with PD. These autoantibodies may contribute to inflammation and oxidative stress in the brain, worsening the disease. However, studies in mouse models show that increasing ACE2 activity can reduce these effects, suggesting that ACE2-based therapies may help mitigate PD symptoms.
 
-Ischemic Stroke (IS): ACE2 is crucial in protecting the brain from stroke-related damage. By converting Ang II into Ang 1-7, ACE2 reduces inflammation and promotes the survival of brain cells. It also enhances nitric oxide production, which helps maintain blood flow to the brain, reducing the severity of strokes.
 
-Depression and Anxiety: ACE2’s role in regulating inflammation and neurotransmitter balance makes it a critical player in mood disorders. Studies show that overexpression of ACE2 in specific brain regions, such as the amygdala, can reduce anxiety-like behaviors by influencing GABAergic transmission, a critical pathway for maintaining emotional balance.
 
ACE2 and Long COVID: A Lasting Neurological Concern
For some COVID-19 patients, neurological symptoms persist long after the initial infection has cleared, a condition known as long COVID. Symptoms such as brain fog, memory loss, and difficulty concentrating have been reported. Researchers suspect that lingering disruptions in ACE2 function may be to blame. During SARS-CoV-2 infection, the virus’s interference with ACE2 can lead to prolonged inflammation and neuronal damage, making recovery slower for some individuals. Future research will need to explore how ACE2’s activity is altered during long COVID and whether therapies that restore its balance could help alleviate these lingering symptoms.
 
Conclusion: Expanding the Role of ACE2 in Neuroscience
ACE2 is far more than just a viral receptor - it plays a crucial role in maintaining neurological health by regulating inflammation, protecting neurons, and ensuring proper blood flow to the brain. The findings discussed in this article reveal ACE2’s potential as a therapeutic target for various neurological diseases, from Alzheimer’s and Parkinson’s to stroke and anxiety disorders.
 
The ongoing research into ACE2, especially in the context of COVID-19, opens new doors for understanding how we can treat or even prevent some of the most debilitating neurological conditions. By continuing to explore ACE2’s many functions in the nervous system, scientists hope to develop more effective therapies for diseases that affect millions worldwide.
 
The study findings were published in the peer-reviewed International Journal of Molecular Sciences (IJMS).
https://www.mdpi.com/1422-0067/25/18/9960
 
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