Angiotensin-converting enzyme 2 (ACE2), a key regulator of the renin-angiotensin system (RAS), maintains central nervous system (CNS) homeostasis by metabolizing neuroinflammatory peptides like angiotensin II (Ang II) and apelin-13, thereby exerting neuroprotective effects. Recent evidence underscores ACE2's paradoxical roles in neurodegeneration: its loss of function due to SARS-CoV-2 spike protein binding exacerbates neuroinflammation and cognitive decline, while its upregulation may mitigate AD pathology by reducing amyloid-β (Aβ) accumulation and tau hyperphosphorylation. The COVID-19 pandemic has further highlighted ACE2 axis dysregulation as a potential accelerator of AD progression, with studies reporting elevated biomarkers of neurodegeneration in post-COVID patients. Therefore, in this review, we highlight the emerging insights into ACE2's dual role in AD and other neurodegenerative diseases, emphasizing its interactions with microglial activation, blood-brain barrier integrity, and mitochondrial dysfunction. We also critically evaluate novel therapeutic strategies, including recombinant ACE2, ACE2-derived peptides, and gene therapy approaches designed to restore RAS balance without compromising viral defense mechanisms. By integrating mechanistic and clinical insights, this work highlights ACE2 as a promising target for neurodegenerative disease interventions.

2025-02-01·Infectious disorders drug targets

Recombinant ACE2 - Opportunities and Challenges in COVID-19 Treatment

Review

作者: Sandhu, Rahul ; Kaur, Mandeep ; Aggarwal, Akriti

It was in 2019 that the world experienced the devastation caused by SARS-COV-2, contributing to a large number of deaths. This contagious virus not only challenged the health care system but has also hit the economy very badly. There has been a lot of research on effective vaccine development, and there has been some success in the same, but no effective antiviral drugs are available in the market. No doubt vaccination can prevent the disease, but it doesn’t have the potential to cure an infected person, for which there is a dire need to develop some effective drug. Angiotensin convertase enzyme 2 (ACE2) played a substantial role in SARS-COV2 pathogenesis and thus has gained much attention during the pandemic. Moreover, it has opened up new avenues for the cure of COVID-19.

2024-11-01·EXPERIMENTAL NEUROLOGY

Unraveling the molecular mechanisms of Ace2-mediated post-COVID-19 cognitive dysfunction through systems genetics approach

Article

作者: Mi, Jia ; Tian, Geng ; He, Hongjie ; Yang, Chunhua ; Zhang, Liyuan ; Huang, Tingting ; Xu, Fuyi ; Lu, Lu ; Wang, Lei

The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.

100 项与 recombinant angiotensin converting enzyme-2 therapies (AntoXa) 相关的药物交易

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