Angiotensin type 2 receptors: Role in aging and neuroinflammation in the substantia nigra

Rodríguez‐Pérez, Ana I.; Garrido‐Gil, Pablo; Pedrosa, M. A.; Garcia-Garrote, María; Valenzuela, Rita; Navarro, Gemma; Franco, Rafael; Labandeira‐Garcia, Jose L.

doi:10.1016/j.bbi.2019.12.011

Cited by 62 publications

(78 citation statements)

References 65 publications

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“…The b-RAS distribution also shows age-related differences. In a recent study, a progressive decrease in the expression of AT 2 Rs with aging was shown in the SN (Rodriguez-Perez et al, 2019). Notably, in the same study, several changes in external appearance, spontaneous motor behavior, RAS components, and pro-oxidative and pro-inflammatory markers were found in young AT 2 R KO mice as being similar to those observed in aged wild type mice.…”

Section: Ras Aging and Frailtysupporting

confidence: 62%

“…Changes in RAS components with age are differently regulated in circulating and local RAS (Abadir, 2011). While circulating RAS components have lower levels in older animals, perhaps, due to age-related increase in blood pressure (Diz, 2008), AT 1 R levels in local RAS are found to be upregulated (Kobori et al, 2007;Abadir, 2011;Abadir et al, 2011;Rodriguez-Perez et al, 2019). Previous work investigating changes in AT 1 R and AT 2 R level with age showed that mitochondrial and nuclear AT 1 R levels increased significantly with age (Gwathmey et al, 2010;Abadir et al, 2011) as opposed to decreased AT 2 R expression (Millan et al, 1991).…”

Section: Ras Aging and Frailtymentioning

confidence: 99%

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Brain Renin–Angiotensin System at the Intersect of Physical and Cognitive Frailty

et al. 2020

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The renin-angiotensin system (RAS) was initially considered to be part of the endocrine system regulating water and electrolyte balance, systemic vascular resistance, blood pressure, and cardiovascular homeostasis. It was later discovered that intracrine and local forms of RAS exist in the brain apart from the endocrine RAS. This brainspecific RAS plays essential roles in brain homeostasis by acting mainly through four angiotensin receptor subtypes; AT 1 R, AT 2 R, MasR, and AT 4 R. These receptors have opposing effects; AT 1 R promotes vasoconstriction, proliferation, inflammation, and oxidative stress while AT 2 R and MasR counteract the effects of AT 1 R. AT 4 R is critical for dopamine and acetylcholine release and mediates learning and memory consolidation. Consequently, aging-associated dysregulation of the angiotensin receptor subtypes may lead to adverse clinical outcomes such as Alzheimer's disease and frailty via excessive oxidative stress, neuroinflammation, endothelial dysfunction, microglial polarization, and alterations in neurotransmitter secretion. In this article, we review the brain RAS from this standpoint. After discussing the functions of individual brain RAS components and their intracellular and intracranial locations, we focus on the relationships among brain RAS, aging, frailty, and specific neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and vascular cognitive impairment, through oxidative stress, neuroinflammation, and vascular dysfunction. Finally, we discuss the effects of RAS-modulating drugs on the brain RAS and their use in novel treatment approaches.

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Section: Ras Aging and Frailtysupporting

confidence: 62%

Section: Ras Aging and Frailtymentioning

confidence: 99%

Brain Renin–Angiotensin System at the Intersect of Physical and Cognitive Frailty

et al. 2020

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“…A possible explanation is that the infection develops as the virus glycoprotein spike binds to ACE2 (angiotensin-converting enzyme 2) receptors. These receptors are widespread in the brain, not only cardiorespiratory centers in the medulla, but also in the dopamine neurons of striatum [8,9].…”

Section: Introductionmentioning

confidence: 99%

COVID-19 and neurological disorders: are neurodegenerative or neuroimmunological diseases more vulnerable?

2020

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Neurological disorders and coronavirus 2019 (COVID-19) pandemic are two conditions with a recent well-documented association. Intriguing evidences showed that COVID-19 infection can modify clinical spectrum of manifested neurological disorders but also it plays a crucial role in the development of future diseases as long-tem consequences. In this viewpoint review, we aimed to assess the vulnerability to SARS-CoV-2 infection and development of COVID-19 among neurological disorders. With this in mind, we tested the hypothesis that age rather than neuropathology itself could be decisive in neurodegenerative diseases such as Parkinson's disease, whereas neuropathology rather than age may be critical in neuroimmunological diseases such as Multiple Sclerosis. Highlighting the role of potential susceptibility or protection factors from this disastrous infection, we also stratify the risk for future neurodegeneration.

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“…4 Angiotensin-converting enzyme 2 (ACE2) receptors are highly expressed in dopamine neurons, and they are reduced in PD because of the degenerative process; therefore, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related brain penetration may cause additional harm and worsen symptoms and may increase the requirement of dopamine replacement therapy, as evident in 5 of our cases. 5,6 Interestingly, the ability of coronaviruses to enter the brain through the nasal cavity determines anosmia/ hyposmia and ageusia in many infected subjects, a symptomatology that closely resembles one of the most prominent premotor symptom of PD. 7 Finally, the dopamine synthetic pathway is possibly involved in the pathophysiology of COVID-19, as ACE2 and dopamine decarboxylase coexpress and coregulate in nonneuronal cell types, which may indicate dopamine depletion and the need for considering levodopa as treatment.…”

mentioning

confidence: 99%

Outcome of Parkinson's Disease Patients Affected by COVID‐19

et al. 2020

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Angiotensin type 2 receptors: Role in aging and neuroinflammation in the substantia nigra

Cited by 62 publications

References 65 publications

Brain Renin–Angiotensin System at the Intersect of Physical and Cognitive Frailty

Brain Renin–Angiotensin System at the Intersect of Physical and Cognitive Frailty

COVID-19 and neurological disorders: are neurodegenerative or neuroimmunological diseases more vulnerable?

Outcome of Parkinson's Disease Patients Affected by COVID‐19

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