Role of brain renin angiotensin system in neurodegeneration: An update

Abstract

a b s t r a c tRenin angiotensin system (RAS) is an endocrine system widely known for its physiological roles in electrolyte homeostasis, body fluid volume regulation and cardiovascular control in peripheral circulation. However, brain RAS is an independent form of RAS expressed locally in the brain, which is known to be involved in brain functions and disorders. There is strong evidence for a major involvement of excessive brain angiotensin converting enzyme (ACE)/Angiotensin II (Ang II)/Angiotensin type-1 receptor (AT-1R) axis in increased activation of oxidative stress, apoptosis and neuroinflammation causing neurodegeneration in several brain disorders. Numerous studies have demonstrated strong neuroprotective effects by blocking AT1R in these brain disorders. Additionally, the angiotensin converting enzyme 2 (ACE2)/Angiotensin (1-7)/Mas receptor (MASR), is another axis of brain RAS which counteracts the damaging effects of ACE/Ang II/AT1R axis on neurons in the brain. Thus, angiotensin II receptor blockers (ARBs) and activation of ACE2/Angiotensin (1-7)/MASR axis may serve as an exciting and novel method for neuroprotection in several neurodegenerative diseases. Here in this review article, we discuss the expression of RAS in the brain and highlight how altered RAS level may cause neurodegeneration. Understanding the pathophysiology of RAS and their links to neurodegeneration has enormous potential to identify potentially effective pharmacological tools to treat neurodegenerative diseases in the brain.

Sinonasal pathophysiology of SARS‐CoV‐2 and COVID‐19: A systematic review of the current evidence

“…6,11,15 ACE2, the necessary cell surface host receptor for SARS-CoV-2, has been previously shown to be expressed on neurons and found to play a role in neurodegeneration. 41 The TMPRSS2 gene, also required for SARS-CoV-2 infection, has not been well studied in the nervous system although one study in a rat model has described expression of TMPRSS2 in neurons of the central nervous system. 42 Previous studies in mice have shown that after intranasal inoculation, the SARS-CoV-1 virus is neuroinvasive with infection directly transmitted through olfactory neurons into the central nervous system.…”

SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications

“…Importantly, there is a RAS in the brain, as well (85). Brain RAS is similar to the other tissue RAS (86). ACE2 has been reported to be expressed specifically in the areas controlling central blood arterial pressure (78).…”

“…In addition, animal model demonstrated that nitric oxide (NO) signaling pathways may also be influenced by ACE2 over-expression in the CNS as demonstrated by an overall reduction of hypertension of neurogenic type in syn-hACE2 mice (78,79,84). Therefore, it has been suggested that since ACE2 possesses a monitoring role in the central regulation of cardiovascular function and blood pressure (86), ACE2 in the brain is a potential therapeutic target for hypertension and other cardiovascular diseases that result from an overactive RAS (80). This fact is significantly crucial in the context of COVID-19 because, apart from pneumonia, COVID-19 leads to acute myocardial injury and, progressively, chronic damage to the cardiovascular system (87).…”

“…Also, ACE2 has a peripheral other than cardio-cerebral vascular protection effect (86,89). The significance of peripheral ACE2 in regulating blood pressure is well-established, but fewer studies emphasize that ACE2 plays a key role in regulating blood pressure (15,16,90).…”

“…Dysregulated brain RAS has been associated with neurodegeneration due to the strong evidence for initiating a cascade of events leading to increase in oxidative stress, apoptosis, and neuroinflammation causing progressively neurodegeneration. Degenerative diseases of the brain that have been linked to altered RAS include Parkinson disease, Alzheimer disease, Huntington disease, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, other than stroke as mentioned above (86,98,99). Moreover, the dysregulation of the antiviral response is another factor that has been associated with neurodegenerative disease (100,101).…”