Biology subjects

Furtado, D. R.

Publications and source records attributed to Furtado, D. R..

4 recordsLinked to original sources

bioRxiv2021

Oligomeric α-Synuclein induces skin degeneration in a reconstructed human epidermis model

Cell senescence may promote epidermal inflammation and degeneration, termed as inflammaging, which is accompanied by keratinocyte loss, resulting in fine lines of wrinkles. Recent findings showed that healthy elderly skin expresses age- and neuron-related amyloidogenic proteins, such as tau, {beta}-Amyloid34, and -synuclein (-Syn), typically found in patients with neurodegenerative diseases. These proteins form toxic aggregates that trigger inflammatory signals. Herein, we investigated the impact of oligomeric -Syn (O-Syn) on the neurosphere (NP) and the reconstructed human epidermis (RHE) 3D models. First, we found the expression of -Syn, {beta}-Amyloid, and amyloid precursor protein (APP) in the RHE. Second, we challenged the RHE and NP with O-Syn, which decreased RHE regeneration, measured by the percentage of cell proliferation and thickness of the stratum basale, but did not affect NP neurite outgrowth. O-Syn did not decrease the number of human neonatal epidermal keratinocytes (HEKn) but, as seen for the RHE, it also decreased the proliferation of HEKn. We confirmed that the oligomeric, and not the monomeric -Syn species, accounted for the proliferation-decreasing effect. O-Syn also increased the NF-kB nuclear translocation in HEKn analyzed by nucleus/cytoplasm NF-{kappa}B fluorescence intensity. In addition, O-Syn triggered inflammation in the RHE, by increasing the mRNA levels of IL-1{beta} and tumor necrosis factor-alpha (TNF-), and the release of TNF- in a time-dependent manner. These findings show that O-Syn does not affect neurite outgrowth but induces a decrease in keratinocyte proliferation along with epidermal inflammation. With our tridimensional models, we demonstrated that the neurodegenerative protein O-Syn also degenerates the epidermis, drawing attention to the need of target-based screening to prevent and treat the effects of skin aging.

neuroscience↗

bioRxiv2021

A cannabinoid receptor agonist shows anti-inflammatory and survival properties in human SARS-CoV-2-infected iPSC-derived cardiomyocytes

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that cause damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the "cytokine storm", strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins 6, 8, 18 and tumor necrosis factor-alpha (TNF-) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.

cell biology↗

bioRxiv2021

Inhibition of SARS-CoV-2 infection in human cardiomyocytes by targeting the Sigma-1 receptor disrupts cytoskeleton architecture and contractility

Heart dysfunction, represented by conditions such as myocarditis and arrhythmia, has been reported in COVID-19 patients. Therapeutic strategies focused on the cardiovascular system, however, remain scarce. The Sigma-1 receptor (S1R) has been recently proposed as a therapeutic target because its inhibition reduces SARS-CoV-2 replication. To investigate the role of S1R in SARS-CoV-2 infection in the heart, we used human cardiomyocytes derived from induced pluripotent stem cells (hiPSC-CM) as an experimental model. Here we show that the S1R antagonist NE-100 decreases SARS-CoV-2 infection and viral replication in hiPSC-CMs. Also, NE-100 reduces cytokine release and cell death associated with infection. Because S1R is involved in cardiac physiology, we investigated the effects of NE-100 in cardiomyocyte morphology and function. We show that NE-100 compromises cytoskeleton integrity and reduces beating frequency, causing contractile impairment. These results show that targeting S1R to challenge SARS-CoV-2 infection may be a useful therapeutic strategy but its detrimental effects in vivo on cardiac function should not be ignored.

cell biology↗

bioRxiv2020

Non-permissive SARS-CoV-2 infection of neural cells in the developing human brain and neurospheres

Coronavirus disease 2019 (COVID-19) was initially described as a viral infection of the respiratory tract. It is now known, however, that several other organs are affected, including the brain. Neurological manifestations such as stroke, encephalitis, and psychiatric conditions have been reported in COVID-19 patients, but the neurotropic potential of the virus is still debated. Herein, we sought to investigate SARS-CoV-2 infection in human neural cells. We demonstrated that SARS-CoV-2 infection of neural tissue is non-permissive, however, it can elicit inflammatory response and cell damage. These findings add to the hypothesis that most of the neural damage caused by SARS-CoV-2 infection is due to a systemic inflammation leading to indirect harmful effects on the central nervous system despite the absence of local viral replication.

neuroscience↗